Elevated Total Protein Research Articles

Cerebrospinal Fluid Parameters in Antisense Oligonucleotide-Treated Adult 5q-Spinal Muscular Atrophy Patients

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

Effects of Combined Ethanol Extract of Anthocleista Vogelii and Alstonia Boonei Stem Barks on Liver Function Indices in Benign Prostatic Hyperplasia Induced

Objective: This study evaluated the effects of combined ethanol extract of Anthocleista vogelii and Alstonia boonei (CEAA) stem barks on the liver function indices of benign prostatic hyperplasia (BPH)-induced rats.Materials and Methods: Thirty (30) male Wistar rats were randomly grouped into five groups (n = 6). BPH was induced subcutaneously with 5 mg/kg/day of testosterone propionate in olive oil. Groups 1-3 served as normal, BPH control (untreated) and standard drug control respectively, while Groups 4 and 5 were BPH-induced rats and treated with 200 and 400 mg/kg/day of the CEAA respectively after one hour of the BPH induction. After twenty-eight days of treatments, biochemical and histopathological analyses were conducted using standard analytical procedures.Results: The acute toxicity result of CEAA indicated no mortality or adverse reactions. Significant body weight change was only observed in the first week from the group-administered 200 mg/kg/day of CEAA. Liver damage was evident in the BPH control characterized by significant (P<0.05) increase in relative liver weight and liver enzymes’ (AST, ALT, ALP) activities but a reduction in total protein and globulin levels. Treatment with CEAA attenuated the liver damage by significantly (P<0.05) reducing the elevated relative liver weight and liver enzyme function activities and elevated total protein and globulin levels.Conclusion: The revealed that the combined ethanol extract of Anthocleista vogelii and Alstonia boonei (CEAA) stem barks possess hepatoprotective effects that could improve liver integrity and functions in BPH induced rats.
 Keywords: Benign prostatic hyperplasia, liver marker indices, Anthocleista vogelii, Alstonia boonei, liver histomorphology

Curcumin protects radiation-induced liver damage in rats through the NF-\u03baB signaling pathway

BackgroundCurcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD).MethodsThirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA).ResultsThe reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days.ConclusionOur study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

Splenic Nodules: Canine Visceral leishmaniasis?

Background: Canine visceral leishmaniasis (CVL) is a parasitic disease of high lethality caused by the protozoan Leishmania infantum in Brazil and is often related to splenomegaly. However, splenic nodules in dogs, although frequent, have not previously been reported as associated with CVL, but with neoplastic diseases. Considering that most dogs infected are oligosymptomatic or asymptomatic and that splenic nodules are common to other diseases, it is prudent to differentially diagnose CVL in view of its high zoonotic potential and lethality. The objective of the study was to describe a case of splenomegaly with splenic nodules associated with CVL in an asymptomatic dog treated with 2% miltefosina. Case: A 5-year-old male Rottweiler with 41 kg, with a history of inappetence, apathy and weight loss was referred to the Veterinary Medicine School Clinic of the Cesmac University Center, Maceió, AL, Brazil. However, during palpation a slight increase in the spleen was noted. Hematological, hemoparasite, biochemical and abdominal ultrasonographic examinations were requested to clarify the clinical suspicion of hemoparasitosis. The hematological and biochemical results respectively showed the following: normocytic normochromic anemia, hyperproteinemia and thrombocytopenia, in addition to hypoalbuminemia, with elevated total protein levels. The test for hemoparasites was negative. Ultrasonography showed mixed echogenicity suggestive of nodules. The rapid test for Ehrlichia, Anaplasma and L. infantum was performed. It was positive only for L. infantum. ELISA, IFAT and qPCR tests were performed to confirm the result. The test showed a cut-off result of 0.371 for ELISA, positive for RIFI at a cut-off of 1:40 and qPCR with less than 1 fg and with amplification above 36 cycles. In view of these results, treatment with 2% miltefosine at a dose of 1 mL/ 10 kg was started once a day, after feeding, for 28 days. The animal was monitored throughout treatment and re-evaluated every 10 days for 30 days, showing signs of clinical development, presenting satisfactory results.Discussion: Canine splenomegaly can be associated with a variety of disease possibilities. In asymptomatic canine visceral leishmaniasis (CanL), the slight increase in spleen and the presence of splenic nodules may lead to a false diagnosis. Splenic nodules may be associated with dogs of advanced age and may be due to lymphoid nodular hyperplasia, which causes nodules with echogenicity, hyperechoic regions with well demarcated irregularity, with centralized hypoechoic areas and an absence of hematological and biochemical alterations. The cause of splenomegaly associated with nodules may be difficult to diagnose and require much time and effort. Therefore, diseases such as visceral leishmaniasis of high lethality must be the priority in differential diagnosis in endemic areas in order to minimize the risk of transmission. In addition to allowing an early intervention aiming at good animal health results and preventive measures, such as the use of repellent collars that reduce the risk of phlebotomo infection. The differential diagnosis of CVL is necessary in endemic areas, even in asymptomatic dogs that may present splenic alterations suggestive of other diseases. Treatment with 2% miltefosine was shown to be, in this case, effective at reducing the splenic nodules and a good alternative for the quality of life of the animal.

Broiler chicken, Fishmeal, Infertile eggs meal, Performance, Carcass, Blood indices

Fishmeal, as animal protein source, is characterised by high cost, dwindling availability and adulteration by feed ingredient suppliers. In view of these, two hundred and ten (210) ten-day old broiler chicks were used, in 2 x 4 experimental layouts, to investigate the effect of replacing fishmeal with infertile egg meal of two forms (with or without shell) and at four graded levels (0, 30, 60 and 100%) on growth performance, haematology, serum biochemistry and carcass indices of broiler chicken. Crude protein (50.2%) and Ether extract (30.6%) were higher in infertile egg without shell (IEM) than in infertile egg withshell (IEMS) (41.36 and 23.4%). Egg forms (IEM or IEMS) did not affect (P>0.05) performance indices measured. Increasing levels of infertile egg meal reduced (P<0.05) body weight gain and final weight without affecting feed conversion ratio (FCR). The IEMS use led to reduction in feed cost (P<0.05) than in IEM. Levels of infertile egg meal reduced (P<0.05) feed cost per body weight gain with least cost at 100% replacement of fishmeal. The IEM elevated (P<0.05) serum total protein, urea and globulin but lowered serum creatinine. Increasing the levels of infertile egg meal lowered blood urea while increasingtotal protein and globulin. Inclusion of IEM at 100% improved Total protein, Albumin and Globulin. The cost of feed reduced (P<0.05) by 13.8% at 100% IEM and IEMS. It was concluded that infertile egg without shell can be used up to 100% in place of fishmeal in broiler chicken diets to reduce feeding cost and improve health without affecting the performance.

Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status

BackgroundThe objective of the study was to assess the cerebrospinal fluid (CSF) findings in COVID-19 patients.AimsThis was an observational retrospective cohort from electronic medical records of hospitalized patients (n = 2655) with confirmed COVID-19 between February 15, 2020, and April 15, 2020, in 182 hospitals from a large health system in the USA. The review of data yielded to a total of 79 patients in 20 hospitals who had CSF analysis.MethodsOutcomes during hospitalization, including hospital length of stay, disease severity, ventilator time, and in-hospital death were recorded. Independent variables collected included patient demographics, diagnoses, laboratory values, and procedures.ResultsA total of 79 patients underwent CSF analysis. Of these, antigen testing was performed in 73 patients. Ten patients had CSF analysis for general markers such as total protein, cell count, glucose, clarity, and color. Seven of the 10 cases (70%) had normal total cell count and normal white blood cell count in CSF. Sixty-three percent (5/8) had elevated total protein. Two patients had normal levels of lactate dehydrogenase (LDH) and 1 patient had significantly elevated (fourfold) neuron-specific enolase (NSE) level in CSF.ConclusionUnlike bacterial infections, viral infections are less likely to cause remarkable changes in CSF glucose, cell count, or protein. Our observations showed no pleocytosis, but mild increase in protein in the CSF of the COVID-19 patients. The fourfold elevation of NSE may have diagnostic/prognostic value as a biomarker in CSF for COVID-19 patients who have altered mental status.Graphical abstract

Cerebrospinal fluid protein in Guillain-Barré syndrome: Need for age-dependent interpretation.

Background and purposeElevated cerebrospinal fluid (CSF) total protein in patients with acute ascending paresis is indicative of Guillain–Barré syndrome (GBS). Recent studies showed that the outdated, but still widely used upper reference limit (URL) for CSF total protein of 0.45 g/L leads to false‐positive results, mainly as a result of lack of age‐adjustment. The objective of this study was to assess the frequency of increased CSF total protein in adult GBS patients according to a new age‐dependent URL.MethodsPatients with GBS treated at the Medical University of Innsbruck between 2000 and 2018 were included in this study. Demographic, clinical, electrophysiological and CSF data were obtained from patients' medical charts. Frequency of increased CSF total protein depending on disease duration was compared using the conventional URL of 0.45 g/L and the age‐dependent URL.ResultsNinety‐seven patients with GBS aged 57 ± 18 years, comprising 38% women, underwent CSF sampling within a median of 6 days after symptom onset. The median CSF total protein concentration was 0.65 g/L and correlated with disease duration. Overall, 74% of patients had elevated CSF total protein levels using the conventional URL, as opposed to 52% applying the age‐dependent URL. At 0–3, 4–7, 8–14 and >14 days after disease onset, elevated CSF total protein was found in 46%, 84%, 78% and 100% of patients using the conventional URL, and in 32%, 53%, 65% and 64% of patients using the age‐dependent URL. In multivariate analysis, significant predictors of elevated CSF total protein were disease duration and the demyelinating GBS variant. Similar results were obtained for CSF/serum albumin quotient (Qalb).ConclusionFewer true‐positives for CSF total protein and Qalb must be considered in suspected GBS, especially in the early disease course.

The reduction of lipid-sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish.

The adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL)-mediated lipolysis play important roles in lipid catabolism. ATGL is considered the central rate-limiting enzyme in the mobilization of fatty acids in mammals. Currently, severe fat accumulation has been commonly detected in farmed fish globally. However, the ATGL-mediated lipolysis and the potential synergy among ATGL, HSL, and autophagy, which is another way for lipid breakdown, have not been intensively understood in fish. In the present study, we added Atglistatin as an ATGL-specific inhibitor into the zebrafish diet and fed to the fish for 5weeks. The results showed that the Atglistatin-treated fish exhibited severe fat deposition, reduced oxygen consumption, and fatty acid β-oxidation, accompanied with increased oxidative stress and inflammation. Furthermore, the Atglistatin-treated fish elevated total and phosphorylation protein expressions of HSL. However, the free fatty acids and lipase activities in organs were still systemically reduced in the Atglistatin-treated fish, and the autophagy marker LC3 was also decreased in the liver. On the other hand, glycogenolysis was stimulated but blood glucose was higher in the Atglistatin-treated fish. The transcriptomic analysis also provided the hint that the protein turnover efficiency in Atglistatin-treated fish was likely to be accelerated, but the protein content in whole fish was not affected. Taken together, ATGL plays crucial roles in energy homeostasis such that its inhibition causes loss of lipid-sourced energy production, which cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients.

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development

ObjectivesTo analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. MethodsPatients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. ResultsCSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. ConclusionPatients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.

Fluted Pumpkin (Telfairia occidentalis) protects against phenyl hydrazine-induced anaemia and associated toxicities in rats

Xenobiotics have been documented to play crucial role in pathogenesis of human diseases. Phenyl hydrazine administration has been associated with hematotoxicity by altering iron metabolism and activating immune response. Telfaria occidentalis is a medicinal plant rich in phytochemicals and minerals that are immune boosters. This study investigated the effect of ethanol leaf extract of T. occidentalis against phenyl hydrazine induced anaemia and associated toxicities in rats. Phenyl hydrazine was exposed to rats through oral administration and ethanol leaf extract of T. occidentalis or vitamin E was administered to ameliorate the toxic effect of the toxicant. This was followed by evaluation of haematological parameters, body weight, and serum protein biomarkers like bilirubin, albumin, total bilirubin. Phenyl hydrazine induced anaemia with significant reduction of blood components like haemoglobin, erythrocytes, leukocytes with concomitant reduction in the body weight of the rat compared to the control. Phenyl hydrazine also compromised serum protein homeostasis as evidenced by elevated serum total protein, albumin, bilirubin and globulin levels. Nevertheless, treatment with ethanol leaf extract of T. occidentalis modulates all the anomalies suggesting its ameliorating effects against phenyl hydrazine-induced anaemia, and may be useful in the treatment/management of chemically induced anaemia or other related diseases.

<p>Lower Gastrointestinal Involvement in Multiple Myeloma: A Case Report</p>

Multiple myeloma (MM) commonly presents with anemia and bone pain. Besides bone marrow involvement, MM has a tendency to involve other organs with gastrointestinal (GI) tract, especially lower GI tract involvement being uncommon. Our case shows an elderly male with anemia due to suspected GI malignancy. Investigations revealed anemia, thrombocytopenia, positive stool occult blood and inconclusive diagnostic endoscopic findings. An elevated serum total protein, serum calcium and serum creatinine gave rise to the suspicion of MM which was later supported by the fulfilment of the CRAB criteria, expressed as hypercalcemia, renal failure, anemia and lytic lesions on skull X-ray. The relationship between multiple myeloma and GI bleeding is rare and indicates extramedullary disease which is a sign of poor prognosis. Early detection may alter the prognostic course of MM.

In vitro Antioxidant and in vivo Hepatoprotective Activities of Root Bark Extract and Solvent Fractions of Croton macrostachyus Hochst. Ex Del. (Euphorbiaceae) on Paracetamol-Induced Liver Damage in Mice.

BackgroundLiver disease is a major public health threat, particularly in developing countries. Several medicinal plants and formulations have been claimed to have liver protective activities. The present study aimed to evaluate in vitro antioxidant and in vivo hepatoprotective activities of root bark extracts of Croton macrostachyus (Euphorbiaceae).MethodsFree radical scavenging activity of crude extract and solvent fractions of the plant was conducted using the DPPH assay method. Hepatoprotective activities of the crude extract and solvent fractions of the plant were carried out based on paracetamol-induced liver damage in mice. Serum biomarkers (AST, ALT, ALP, total bilirubin and total protein) were assessed to find out the effect. Histopathological examination was also carried out for all groups of mice to further confirm the findings.ResultsAntioxidant assay revealed that the crude extract, aqueous fraction and chloroform fraction of Croton macrostachyus exhibited free radical scavenging activity with IC50 values of 128.6, 168.9, and 406 µg/mL, respectively. Pretreatment of the mice with the crude extract and solvent fractions of Croton macrostachyus significantly reduced ALP (p<0.001), ALT (p<0.001), and AST (p<0.001) levels at all the administered doses compared to the toxic group. The crude extract and chloroform fraction decreased total bilirubin level at doses of 200 mg/kg (P<0.05) and 400 mg/kg (P<0.001). Pretreatment of the mice with 400 mg/kg of the crude extract and aqueous fraction elevated total protein value compared to the paracetamol treated group (P<0.05). The hepatoprotective activities of the plant extracts were confirmed by histopathological studies.ConclusionFrom this study, it can be concluded that the crude extract and solvent fractions of Croton macrostachyus demonstrated antioxidant and hepatoprotective activities.

Impact of dietary vitamin c on plasma metabolites, antioxidant capacity and innate immunocompetence in juvenile largemouth bass, Micropterus salmoides

The present study aimed to investigate the effects of dietary vitamin c on plasma metabolites, antioxidant capacity and innate immunocompetence in juvenile largemouth bass. To achieve this, the fish were fed diets supplemented with 0 (basal), 25, 50, 75, 100, 125, 150, and 175 mg/kg dietary VC for 60 day. Then, fish were sampled and tissues were collected to determine antioxidant capacity and innate immunity. Also, post bacteria challenge evaluations were carried out. In the present study, hemorrhagic lip, hemorrhagic fin, dark skin coloration, eroded fin and scoliosis were observed in AMP0 group. Dietary VC (AMP125, AMP150 and AMP175) significantly elevated plasma high density lipoprotein cholesterol, total protein and endogenous antioxidant enzyme activity and their hepatic mRNA level (superoxide dismutase, glutathione peroxidase and catalase), these treatments also lowered low density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase concentration and Malondialdehyde. In addition, AMP125 and AMP150 significantly enhanced immune parameters (C3, C4 and IgM).Conclusively, dietary VC triggers antioxidant system, prevent oxidative stress and enhances some innate immune components. Moreover, dietary VC improves liver integrity and percentage survival rate during Aeromonas hydrophila infection. Dietary VC administration at 125–150 mg/kg is suitable to enhance antioxidant and immune capacity in largemouth bass without negative effects on the growth and feed utilization efficiency.

Antioxidant and hepatoprotective potentials of active fractions of Lannea barteri Oliv. (Anarcadiaceae) in rats

IntroductionLannea barteri is used in the folkloric treatment of many disease states ranging from epilepsy, diarrhoea, oedema and ulcers, etc. This study investigated the antioxidant and hepatoprotective potentials of methanol (MFLB), n-hexane (nHFLB) and ethyl acetate (EFLB) leaf fractions of L. barteri and identified the active metabolites. Materials and methodsThe in vitro models used were 1, 1-diphenyl-1-picrylhydrazyl (DPPH), reducing power and thiobarbituric acid assays while in the in vivo model, carbon tetrachloride-induced oxidative liver damage in albino rats was used, and the biomarkers assayed were aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), serum total protein, serum direct and total bilirubin. Also, histopathological examination of the liver, high performance liquid chromatography (HPLC) profiling and liquid chromatography-mass spectroscopy-electrospray ionization (LC-MS-ESI) analysis of the fractions were done. ResultsIn the in vitro assays, the decreasing order of DPPH free radical scavenging activity of the ascorbic acid and fractions at 400 μg/ml is as follows: ascorbic acid (86.6%), MFLB (52.8%), EFLB (36.6%), and nHFLB (28.1%). The percentage scavenging activity of the samples at 400 μg/ml in the TBA followed this pattern: ascorbic acid (117.1%), MFLB (82.2%), nHFLB (80.0%), and EFLB (46.9%). The ascorbic acid elicited highest reducing power (42.6%), followed by MFLB (22.5%), nHFLB (13.7%), and EFLB (-0.93%). The in vivo study showed significant (p < 0.0001) reduction in serum AST, ALT, and direct bilirubin with a non-significant reduction in ALP, total bilirubin and MDA, and mild elevation in total protein. Histopathological studies revealed a restorative effect on liver architecture. The phytochemical analyses revealed the presence of resins, terpenoids, flavonoids, carbohydrates, alkaloids, reducing sugar, saponins, tannins and proteins. HPLC-ESI-MS analysis revealed the presence of potentially bioactive compounds in L. barteri fractions. ConclusionThe fractions from L. barteri leaf possessed in vitro antioxidant and hepatoprotective potentials against CCl4-hepatic oxidative damage; therefore, proper isolation and characterization of these identified bioactive compounds responsible for the observed effects are ongoing.

Distinguishing neurosarcoidosis from multiple sclerosis based on CSF analysis: A retrospective study.

To characterize a cohort of patients with neurosarcoidosis with particular focus on CSF analysis and to investigate whether CSF values could help in distinguishing it from multiple sclerosis (MS). This retrospective cohort study enrolled 85 patients with a diagnosis of neurosarcoidosis (possible, probable, or definite). CSF total protein, white cell count, and angiotensin-converting enzyme levels were measured. CSF and serum oligoclonal immunoglobulin G (IgG) patterns were analyzed with the use of odds ratios and binary logistic regression. Eighty patients had a probable (nonneural positive histology) or definite (neural positive histology) diagnosis of neurosarcoidosis. Most frequent findings on MRI were leptomeningeal enhancement (35%) and white matter and spinal cord involvement (30% and 23%). PET scan showed avid areas in 74% of cases. CSF analysis frequently showed lymphocytosis (63%) and elevated protein (62%), but CSF-selective oligoclonal bands were rare (3%). Serum ACE levels were elevated in 51% of patients but in only 14% of those with isolated neurosarcoidosis. Elevated CSF ACE was not found in any patient. Large elevations in total protein, white cell count, and serum ACE occur in neurosarcoidosis but are rare in MS. The diagnostic use of these tests is, however, limited because minimal changes may occur in both. MS clinical mimics in neurosarcoidosis are not common, and intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is rare in neurosarcoidosis but occurs in 95% to 98% cases of MS. We suggest caution in making a diagnosis of neurosarcoidosis when intrathecal oligoclonal IgG synthesis is found.

Maxillomandibular Deformity in a Canine with Fibrous Osteodystrophy Secondary to Chronic Kidney Disease

Background: Cases of renal fibrous osteodystrophy are usually associated with nutritional causes, which of renal causes are considered uncommon in dogs. This disorder is characterized by the intense proliferation of fibrous connective tissue in bones, impairing bone stiffness. The aim of this study was to report a case of fibrous osteodystrophy secondary to chronic kidney disease in a canine with a "rubber jaw" facial deformity.Case: A 4-year-old male unneutered mongrel dog weighing 5.2 kg had a history of apathy, progressive weight loss and vomiting for one month, and polyuria and polydipsia for more than three months. In addition, the owner complained about the deformed appearance in the muzzle region of the animal, which was evidenced flexibility of the same, with a displacement of the mandible and maxilla on physical examination, similar to the "rubber jaw". Blood tests revealed macrocytic anemia, elevated total plasma proteins, and lymphopenia-associated neutrophilia, as well as hyperphosphatemia (24 mg/dL), uremia (283.6 mg/dL) and increased creatinine (8.6 mg/dL), ALT (143.2 UI/L) and alkaline phosphatase (3222.2 UI/L), while calcium (8.8 mg/dL) and albumin (1.9 g/dL) were decreased. A serological test for visceral leishmaniasis was also performed, which was negative. Abdominal ultrasound imaging revealed kidneys with alterations in tissue architecture, increased thickness and complete loss of cortico-medullary relationship, while the parathyroid gland was enlarged and spindle-shaped. Cranial radiography showed marked radiopacity of the bilateral maxillary bones, with destruction of the nasal, turbinate and frontal bones, as well as loosening of the teeth and destruction of the mandibular bone matrix, characterizing an aspect of “rubber jaw”. Based on the history, history and evidence of azotemia, hyperphosphatemia and loss of facial bone density, the diagnosis of fibrous osteodystrophy secondary to chronic kidney disease associated with hyperparathyroidism was concluded.Discussion: The clinical and laboratory findings reported in the present study were similar to those described in dogs with renal fibrous osteodystrophy associated with hyperparathyroidism. In the presence of azotemia, the patient was in stage 4 of chronic kidney disease which, despite investigating the infectious etiology, which was negative, remained unknown. Along with chronic kidney disease, the observation of hyperphosphatemia associated with hypokalemia contributed to the clinical investigation, whose pathophysiological mechanisms of this disorder were discussed in this study. The organic alterations observed in the patient's imaging examination coincided with the pathophysiological processes of renal fibrous osteodystrophy. The findings of renal and parathyroid alterations on ultrasound, as well as the damage to the bone matrix, maxillomandibular deformity and loss of bone support evidenced on cranial radiography, led to the conclusion of the diagnosis of renal fibrous osteodystrophy secondary to hyperparathyroidism. Despite the recommended symptomatic therapy, the patient died within 24 hours of hospitalization, and it was not possible to perform a necropsy. This report is highlighted by the occurrence of bone deformity at the maxillary and mandibular level, as a result of renal dysfunction in a young canine, alerting to the importance of complementary exams for proper diagnosis.

Upregulation of mitochondrial E3 ubiquitin ligase 1 in rat heart contributes to ischemia/reperfusion injury.

Mitochondrial dysfunctions are responsible for myocardial injury upon ischemia/reperfusion (I/R), and mitochondrial E3 ubiquitin ligase 1 (Mul1) plays an important role in maintaining mitochondrial functions. This study aims to explore the function of Mul1 in myocardial I/R injury and the underlying mechanisms. The Sprague-Dawley rat hearts were subjected to 1 h of ischemia plus 3 h of reperfusion, which showed the I/R injury (increase in infarct size and creatine kinase release) and the elevated total and mitochondrial protein levels of Mul1 and p53 accompanied by the enhanced interactions between Mul1 and p53 as well as p53 and small a ubiquitin-like modifier (SUMO1). Consistently, hypoxia/reoxygenation (H/R) treated cardiac (H9c2) cells displayed cellular injury (apoptosis and necrosis), upregulation of total and mitochondrial protein levels of Mul1 and p53, and enhanced interactions between p53 and SUMO1 concomitant with mitochondrial dysfunctions (an increase in mitochondrial membrane potential and reactive oxygen species production with a decrease in ATP production); these phenomena were attenuated by knockdown of Mul1 expression. Based on these observations, we conclude that a novel role of Mul1 has been identified in the myocardial mitochondria, where Mul1 stabilizes and activates p53 through its function of SUMOylation following I/R, leading to p53-mediated mitochondrial dysfunction and cell death.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

An Institutional Retrospective Study on Recognizing the Delay in Multiple Myeloma Diagnosis

Background Multiple myeloma (MM) is the abnormal proliferation of plasma cells in the bone marrow often resulting in debilitating symptoms ranging from ostealgia to pathological fractures from bone destruction. According to American Cancer Society, MM accounts for 1-2% of cancers and approximately 17% of hematological malignancies in the United States each year (1). Fifty percent of patients with symptomatic MM have three or more primary care visits before they are referred to a specialist, which is greater than any other cancer (5). It has been shown that a delay in diagnosing multiple myeloma negatively impacts the clinical course of the disease and hence the outcome in patients (2). Patients with longer diagnostic intervals also experience shorter disease free survival and more complications from treatment (4). Herein, a retrospective analysis was performed to determine the average delay in diagnosis of MM. Methods This is a retrospective electronic chart review of all indexed newly diagnosed MM cases between 1/1/2014 through 12/31/2018 at New York-Presbyterian Brooklyn Methodist Hospital (NYP BHM). NYP BMH is a Weill Cornell Medical College-affiliated hospital in Brooklyn, NY whose patient population includes those with private insurance, uninsured and Medicare/Medicaid. Data abstraction from the electronic medical record (EMR) was uniform and involved baseline characteristics such as age, gender and race. International Classification of Diseases (ICD)-10-CM code (C90.00) was used for extraction of data which identified 492 patients. After excluding patients with MGUS or a prior diagnosis of multiple myeloma, 104 patients were included in the final study. We calculated the number of days between the date of first abnormal laboratory value seen on bloodwork for a myeloma related sign (at least 90 days prior to diagnosis) to the date of bone marrow biopsy that confirmed the diagnosis. The inclusion criteria were anemia defined as hemoglobin &amp;lt;12gm/dl, Hypercalcemia defined by corrected calcium &amp;gt;10, kidney dysfunction with a creatinine &amp;gt;1.5 and total protein &amp;gt;8. Results Of the 104 patients with newly diagnosed MM, 69 patients were diagnosed within 90 days of the first abnormal lab value recorded in our electronic medical record (EMR). Thirty-five patients (34%) had a delay in diagnosis at least 90 days with a mean delay of 38 months. Isolated anemia was the most common abnormal lab finding with 29/104 (28%) having documented anemia at least 90 days prior to diagnosis of myeloma. The mean delay in diagnosis for patients with anemia was 41 months. There were four patients with anemia and elevated creatinine with an average delay of 23 months. Five patients had anemia and elevated calcium with an average delay of 21 months. Nine patients had anemia and elevated total protein with an average delay of 38 months. Conclusion: In the current era where we have effective therapies for MM it is now more important than ever to avoid a delay in diagnosis. We demonstrate that 34% of patients receiving care at an Urban Teaching Hospital had at least a 90 day delay in their diagnosis of MM. Our cohort consisted of 64% African Americans, suggesting that minorities are more commonly affected by this. There is a need for more awareness amongst clinicians to consider the diagnosis of MM in the workup of anemia.

Elevated cerebrospinal fluid levels of total protein in patients with secondary central nervous system vasculitis and giant cell arteritis

Objectives: Secondary central nervous system vasculitis (SCNSV) is an extremely rare, refractory, and fatal disease in patients with giant cell arteritis (GCA). We compared the characteristics of GCA patients with and without SCNSV.Methods: This retrospective, single-center, observational cohort study included 35 patients with GCA admitted to Juntendo University Hospital from April 2009 to March 2019. The primary outcome was all-cause mortality.Results: We diagnosed four patients with GCA and SCNSV (SCNSV group) and 31 patients with GCA but no SCNSV (non-SCNSV group). The mortality rate of the SCNSV and non-SCNSV groups was 100% and 10%, respectively (p = .001). The SCNSV group had lower serum levels of C-reactive protein at the time of GCA diagnosis and higher cerebrospinal fluid (CSF) levels of total protein (102 mg/dL vs. 38 mg/dL, p = .008) and albumin (66 mg/dL vs. 21 mg/dL, p = .008) at the time of SCNSV diagnosis.Conclusion: At the time of SCNSV diagnosis, GCA patients had elevated CSF total protein and albumin levels. CSF examination in GCA patients suspected of having SCNSV may be useful for early diagnosis of SCNSV.