Significant Elevation In Serum Research Articles

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Hepatorenal and Testicular Dysfunctions of Clodinafop-Propargyl Bait in Male Black Rat, Rattus rattus and Its Field Efficiency

) has become in a commensal relationship with humans and has been responsible for obvious damage to agriculture annually. In this study, clodinafop-propargyl bait (0.98%) was introduced to the adult male rats for seven days under laboratory conditions using a non-choice feeding method. The impact of the compound on the body and some organs' weights and functions was studied. Histopathological changes of the liver, kidney, and testis as well as sperm count, sperm morphology, vitality and motility percent were recorded. The efficiency of clodinafop-propargyl bait (0.98%) was evaluated under field conditions of crop stores. The results demonstrated that the body weight and testis of rats significantly decreased obviously after treatment. As well as, the treatment caused immoderate loss of water through the skin, losing appetite and slow movement of rats. While weights of the liver and kidney of treated rats significantly increased. In addition, the appearance of morphological and histopathological alterations in the liver, kidneys, and testis were observed. Also, significant elevation in serum (ALT and AST) enzymes, urea, creatinine and uric acid levels compared with control after treatment were recorded. Furthermore, sperm count, motility and vitality percentages significantly decreased (p≤0.05) in treated rats compared with controls. There were perspicuous abnormalities in the form of the head, neck, and tail of the spermatozoa in the treated rats. Regarding, sperm motility; non-progressive and immotile grades were significantly increased in treated rats compared with controls. Moreover, clodinafop-propargyl bait (0.98%) proved efficient under crop store conditions as it caused an 86.78 % reduction in the rat population. In conclusion, clodinafop-propargyl bait has a strong toxic impact on the liver, kidneys and reproductive system of male black rats affecting their fertility by destroying testicular integrity and function. Furthermore, the field results proved these impacts and achieved good results. We can conclude that this compound can be used in the control of black rats and can be used in rodent control programs.

Assessment of Serum and Tissue YKL-40 in Egyptian Psoriasis Vulgaris Patients versus Controls

Abstract Background Psoriasis is an inflammatory, papulosquamous disease of the skin. Serum YKL-40 is a useful biomarker of inflammation in psoriasis as well as other inflammatory diseases. Objectives To compare the levels of serum and tissue YKL-40 as a reliable biomarker of inflammation in psoriasis vulgaris patients versus controls. Patients and methods We performed a case-control study in 30 Egyptian patients with psoriasis vulgaris and 30 controls. Cases and controls were selected excluding pregnant females, individuals with any malignancies, patients who received systemic treatment for psoriasis for 1 month prior to their inclusion in the study and patients who received topical treatment for psoriasis 2 weeks prior to their inclusion in the study. The serum &amp; tissue levels of YKL-40 were measured using ELISA technique. Results Both the serum and tissue levels of YKL-40 were elevated in psoriasis patients when compared with controls (p &amp;lt; 0.01). These levels correlated highly with PASI score; both serum and tissue YKl-40 levels were significantly higher in patients with moderate psoriasis as compared with those with mild psoriasis. On the other hand, there was no statistical correlation between the serum and tissue levels of YKL-40 and age, BMI or disease duration. Conclusion The significant elevation in serum and tissue levels of YKl-40 in psoriatic patients when compared with healthy controls validates the marker in question as a reliable biomarker of inflammation in psoriasis vulgaris patients.

Ameliorative Effect of Propolis Against Thioacetamide Induced Hepatorenal Injury in Adult Male Rats. Kidney Injury Molecule-1 (KIM-1) a Biomarker of Renal Injury

Abstract Background: Thioacetamide (TAA), a known industrial toxic agent, is extensively used in animal studies for induction of hepatic necrosis, fibrosis and cirrhosis, also reported to be nephrotoxic through induction of oxidative stress. Propolis, bee glue, is known by its antioxidant and anti-inflammatory properties. Aim of Study: This work aimed to evaluate the potential protective effect of propolis on TAA-induced hepatorenal damage and to evaluate the efficacy of Kidney Injury Molecuole-1 (KIM-1) in early detection of renal injury. Material and Methods: This study was performed on 24 adult male albino rats, divided into 3 groups; (I) Control group, (II) TAA-group (TAA was given in a dose of 50mg/kg /day intraperitoneally, 5 days/week for 2 weeks), (III) TAA-propolis treated group (TAA was given in the same way as in TAA-group, propolis was given in a dose of 500mg/kg/day by gavage, 5 days/week for 2 weeks). All studied rats were subjected to determination of initial and final body weight, body weight percent change, absolute and relative liver and kidney weight, as well as assessment of hepatic function by serum Alanine Transaminase (ALT) and Aspartate Transam-inase (AST), renal function by serum urea, creatinine and potassium (K+) level, with determination of renal tissue oxidative stress markers; Malondialdehyde (MDA) and Glu-tathione-S-Transferase (GST), inflammatory marker; Mye-loperoxidase (MPO), renal tissue damage marker; Kidney Injury Molecule-1 (KIM-1). In addition, specimens of liver and kidney were taken and processed for light microscopic studies. Results: TAA induced hepatotoxic and nephrotoxic effect that was evident by the significantly increased serum ALT, AST, urea and creatinine, with significant decrease in serum K+ level as well as significantly increased renal tissue MDA, GST, MPO and KIM-1 when compared with control group. Treatment with propolis caused significant reduction in serum ALT, AST, urea and creatinine, with significant elevation in serum K+ as well as significant reduction in renal tissue MDA, GST, MPO and KIM-1 when compared to the TAA group, but still significantly higher compared to controls except for urea. These results were confirmed by the histopathological findings. Conclusion: Propolis could partially ameliorate the TAA induced hepatorenal damage, which might be related to attenuation of oxidative stress and inflammation. Moreover, KIM-1 could be beneficial in detection of renal injury.

Hypolipidemic Effect of Apigenin Extracted From Parsley (Petroselinum sativum L.) Leaves In Cadmium Chloride Treated Rats (Part II)

Cadmium has been reported to have cumulative effects on mortality ,cardiovascular , renal and neurologic .flavonoids (apigenin) are naturally occurring phytochemicals possessed divers pharmacological effects hypolipidemic and antioxidant activity .this study was carried out to investigate the protective effect of the flavonoids extracted from (Petroselinum sativum) parsley leaves on some parameters related to cardiac risk in adult male rats exposed to 50 ppb cadmium chloride in drinking water . Crude flavonoids were extracted from parsley leaves . Further purification of flavonoids was performed by gel permeation column chromatography (TLC) . Thirty adult Albino male rats randomly and equally divided into three group (10 rats for each) and were treated daily for 60 days as follows : The rats were kept on ordinary tab water as control (group c) , received drinking water containing 50 ppb of cadmium chloride (group T1) and simultaneously given orally 150mg/kg B.W. of flavonoids (apigenin) extracted from parsley in addition to 50ppb of cadmium chloride in drinking water (group T2). Fasting blood sample were collected by cardiac puncture technique at 0,30 and 60 days of experiment for measuring the flowing parameters : serum lipid profile including: a. triacylglycerol (TAG) .b. serum total cholesterol (TC) .c. serum high density lipoprotein (HDL-C). d. serum low density lipoprotein (LDL-C).e. serum very low density lipoprotein (VLDL-C) concentration .Besides section from heart, aorta were taken at the end of experiment for histopathological study .The results showed that the yield of crude flavonoids from parsley leaves were approximately 2.68% of dray leaves .Purification of crude flavonoids on Sephadex LH-20 clarified three peaks activity and the proportions of the purified fraction P1, P2 and P3 were 14.06, 82.43 and 3.5% respectively. Thin layer chromatography confirmed that p2 was pure apigenin . the result revealed that animal exposed to 50 ppb of cdcl2 water for 60 days caused cardiac damage manifested by a significant elevation in serum TC,TAG,HDL-C,VLDL-C and LDL-C concentrations, with a significant depression in serum HDL-C concentration . Gavage of flavonoids and Cd concurrently caused a significant correction of the previous studies parameters . Histological section of the heart and aorta of cd treated (T1) group revealed an occurrence of early signs of atherosclerotic lesions . Such histological change could not be observed in heart and aorta of animal in group T2 after oral intubation of flavonoids (apigenin). It could be concluded that apigenin is effective in prevention the deleterious effect of cadmium chloride on major rick factors of cardiovascular system.

Interleukin-1β, interleukin-6 and tumour necrosis factor-alpha levels in blood and saliva in hypothyroidism accompanied with periodontitis

Relationship between thyroid dysfunction and periodontal disease has been mediated through an immune response. Cytokines are implicated in the initiation, consequences of immune response and a crucial role in the pathogenesis of thyroid disease, directly target thyroid follicular cells; and in the development and progression of periodontitis. This study aimed to detect cytokines levels which known to be associated with periodontitis in serum and saliva, to test the hypothesis that hypothyroidism influences the levels of biomarkers of periodontitis. Samples were collected from sixty patients with hypothyroid age ranged (20-64) years, thirty of patients were without periodontitis (group I) and 30 with periodontal disease (II); moreover, 30 subjects considered as control (group III) with age (20-53) years. Detection of cytokines was performed by ELISA. The results showed a significant elevation in serum and salivary levels of IL-1β (P&lt;0.001) among patients’ groups (I and II) as compared to group III, as well IL-1β increase significantly in group II (P&lt;0.001) than in group I and also than group III. There are non-significant differences (P&gt;0.05) in serum level of IL-6 and TNF-α and salivary levels of TNF-α among all study groups. Nevertheless, the salivary level of IL-6 is increased significantly (P&lt;0.05) in group II as compared with group I and group III, and their non-significant differences (P&lt;0.05) between groups I and III. The present finding proposed that hypothyroidism might encourage periodontitis development; as well as serum and salivary levels of IL-1β, with salivary IL-6 may represent important biomarkers for the early detection of periodontitis in hypothyroid patients.

Nigella sativa and Aloe vera protection against doxorubicin hepatotoxicity

Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited due to its significant toxicity to most tissues and organs. Administration of DOX induced acute hepatotoxicity manifested by significant elevation in serum and liver lipid peroxidation. The present study was designed to evaluate and confirm the protective effect of Nigella sativa (N.S), Aloe vera (A.V) and their mixture. A cumulative dose (30 mg/kg i.p.) of DOX divided into 6 equal doses administered over six weeks to male albino rats separate or combined with N.S, A.V or their mixture extract. At the end of the experiment, biochemical and histological parameters were assessed. Concerning oxidative stress and antioxidant defense system, the depleted hepatic glutathione content (GSH) of DOX-administered rats as well as glutathione peroxidase (GPx), catalase (CAT) and super oxide dismutase (SOD) activities were increased above normal levels as a result of pretreatment with N.S, A.V and their mixture. However, while elevated lipid peroxidation was noticed in DOX treated rats, pretreatment with N.S, A.V and their mixture produced a detectable decrease in the lipid peroxidation level. Histological measurements showed that DOX caused a marked rise multiple focal coagulative necrosis of hepatocytes associated with hemorrhage while rats pretreated with N.S, A.V and their mixture in combination with DOX showed no histopathological changes compared to normal control. From these data, it can be concluded that N.S, A.V and their mixture of extracts could be protective for the liver cells against DOX-induced hepatotoxicity due to their contents of polyphenolic compounds that might serve as novel adjuvant therapy with DOX.

Parathyroid hormone 1 receptor is essential to induce FGF23 production and maintain systemic mineral ion homeostasis

Parathyroid-hormone-type 1 receptor (PTH1R) is extensively expressed in key regulatory organs for systemic mineral ion homeostasis, including kidney and bone. We investigated the bone-specific functions of PTH1R in modulating mineral ion homeostasis by generating a novel mouse model in which PTH1R is ablated in the limb mesenchyme using Prx1Cre transgenic mice. Such ablation decreased FGF23 protein and serum levels by 50%, despite normal Fgf23 mRNA levels in long bones. Circulating calcium and PTH levels were unchanged, but inorganic phosphate and 1,25(OH)2D3 levels were significantly decreased and accompanied by elevated urinary calcium and phosphate wasting. Key renal genes for balancing mineral ion homeostasis, calbindinD28k, Klotho, and Napi2a were suppressed by 30-40%. Intermittent hPTH(1-34) injections increased Fgf23 mRNA (7.3-fold), Nurr1 mRNA (3.1-fold), and serum intact-FGF23 (1.6-fold) in controls, but failed to induce Fgf23, Nurr1 mRNA, or intact FGF23 production in mutants. Moreover, a significant elevation in serum C-terminal-FGF23 levels (4-fold) was detected in both genotypes. PTH markedly downregulated Galnt3 expression (2.7-fold) in controls but not in mutants. These results demonstrate the pivotal role of PTH1R in long bones to regulate systemic mineral ion homeostasis and the direct induction of FGF23 by PTH1R signaling.

Rutin rich Emblica officinalis Geart. fruit extract ameliorates inflammation in the pancreas of rats subjected to alcohol and cerulein administration

The modulating effect of methanolic extract of Emblica officinalis (MEEO) on ethanol (EtOH)- and cerulein (Cer)-induced pancreatitis in rats was investigated in this study. Male albino Wistar rats were divided into four groups. Group 1 and 2 rats served as control and fed normal diet. Group 3 and 4 rats were fed isocalorically adjusted diet containing EtOH (36% of total calories) for 5 weeks and also subjected to intraperitoneal injection of Cer 20 µg/kg b.wt. thrice weekly for the last 3 weeks of the experimental period. In addition, group 2 and 4 rats received 200 mg/kg b.wt. of MEEO from 15th day till the experimental period. Serum levels of lipase (L), amylase (A), cytokines IL-1β, IL-18, caspase-1 and oxidative stress index (OSI) were determined. Levels of fecal trypsin, total collagen, caspase-1, myeloperoxidase (MPO), antioxidants and mRNA expression of caspase-1, IL-1β and IL-18 were determined in the pancreas. HPLC analysis showed the presence of rutin in MEEO. We observed a significant elevation in serum L/A ratio, IL-1β, IL-18, caspase-1, OSI, collagen, MPO activity and the mRNA expression of IL-1β, IL-18 and caspase-1 and significant reduction in fecal trypsin and antioxidant status in EtOH- and Cer-administered rats. The inflammatory markers were found to be reduced and the antioxidant status of pancreas was maintained in MEEO-coadministered rats. The rutin rich nature of E. officinalis can be claimed for its anti-inflammatory and pancreato protective effects.

Peripheral Tissue Trauma Triggers an Inflammatory Response Causing Intestinal Microvascular Serum Leak Which Disrupts Gastrointestinal Motility

Introduction: Combat and civilian trauma is the leading cause of death for individuals in the prime of their life. Gastrointestinal dysfunction plays a key role in the detrimental sequelae of trauma (systemic inflammatory response, feeding intolerance, reflux/aspiration pneumonia and bacterial overgrowth/dissemination through mucosal barrier failure), but the mechanisms through which peripheral tissue injury can induce these responses is unclear. Aims: To investigate the mechanism of trauma-induced gastrointestinal dysfunction in a precisely controllable non-narcotic, tissue-bone matrix (TBX) trauma model, which is known to reproducibly display significant gastrointestinal dysmotility. Methods: A non-narcotic murine tissue trauma model was constructed by the dorsal subcutaneous implantation of minced donor syngeneic tissue-bone matrix (TBX) precisely adjusted to 17.5% body weight and studied after 21 hrs. Inflammatory mediators in serum, fresh TBX and TBX wound fluid at 21hrs were measured by electrochemiluminescence detection and intestinal muscularis microvascular leak was microscopically quantified in whole-mounts after i.v. injection of FITC-dextran (70k MW). Gastrointestinal transit and jejunal circular muscle contractility was assessed after injection of normal mouse serum (i.p. 100μl q1h x 8). Results: Compared to normal serum, TNF α was only acutely elevated in fresh TBX fluid (1.1±0.01, 4.1±0.22 and 1.1±0.01 ng/ml) and IL 1β exhibited increased levels in both fresh TBX fluid and in TBX wound fluid (1.9±0.22, 107.6±1.45 and 92.2±6.12 ng/ml). Whereas, IL-6 (80.4±10.0, 158.5±4.08 and 26851.1±4883.39 ng/ml) and kerotinocyte chemokine (KC; 237.5±47.14, 110.4±1.59 and 9763.2±817.29 ng/ml) were significantly increased in the re-harvested TBX wound fluid after 21 hours of implantation. The systemic response to the implanted TBX resulted in significant serum elevations in IL-6, KC and IL-10 compared to control and sham surgical groups at 21 hrs (N=6 each), as well as causing significant intestinal muscularis microvascular leak. Interestingly, i.p. injections of normal serum into naive mice recapitulated the TBX-induced dysmotility causing delayed gastrointestinal transit (9.8±0.15 vs. 3.4±0.22) and a 49.5% suppression in bethanechol stimulated jejunal muscle strip contractility compared to saline injections (N=6). Conclusion: Peripheral tissue injury and consequent systemic inflammatory response cause intestinal muscularis microvascular leak and dysmotility, which can be recapitulated by intraperitoneal injection of exogenous normal serum. These novel findings demonstrate the key regulatory effect of intestinalmicrovascular leak on gastrointestinal motility in trauma.

Novel model of peripheral tissue trauma-induced inflammation and gastrointestinal dysmotility

Trauma is a leading cause of death and although the gut is recognized as the 'motor' of post-traumatic systemic inflammatory response syndrome and multiple organ failure, studies on the gastrointestinal (GI) tract are few. Our objectives were to create a precisely controllable tissue injury model in which GI motility, systemic inflammation and wound fluid can be analyzed. A non-narcotic murine trauma model was developed by the subcutaneous dorsal trans-implantation of a devitalized donor syngeneic harvested tissue-bone matrix (TBX), which was precisely adjusted to % total body weight and studied after 21 h. Gastrointestinal transit histograms were plotted after the oral administration of non-digestible FITC-dextran and geometric centers calculated. Organ bath evaluated jejunal circular muscle contractility. Multiplex electrochemiluminescence measurements of serum and TBX wound fluid inflammatory mediators were performed. Increasing TBX amounts progressively delayed transit, whereas TBX heat denaturation or decellularization prevented ileus and death. In the TBX(17.5%) model, jejunal muscle contractility was suppressed and a systemic inflammatory response developed as significant serum elevations in IL-6, keratinocyte cytokine and IL-10 compared to sham. In addition, inflammatory responses within the wound fluid showed elevated levels of preformed IL-1β and TNF-α, whereas, 21 h after implantation IL-1β, IL-6 and keratinocyte cytokine were significantly increased in the wound. A novel donor tissue-bone matrix trauma model was developed that is precisely adjustable and recapitulates important clinical phenomena. The non-narcotic model demonstrated that increasing tissue injury progressively caused ileus, initiated a systemic inflammatory response and developed inflammatory changes within the wound.

Evaluation of serum parathyroid hormone‐related peptide in hyperthyroid patients

Hypercalcemia occurs in 10-20% of patients with hyperthyroidism, but its pathogenesis is still unclear. To evaluate changes in parathyroid hormone-related peptide (PTH-rP) concentration in hyperthyroid patients compared with healthy controls. We studied PTH-rP, parathormone (PTH) and ionized calcium levels in 153 hyperthyroid patients, and 89 control subjects. These variables were revaluated after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months in a subgroup of 47 patients. Pretreatment PTH-rP and ionized calcium level were significantly higher in hyperthyroid patients than in controls, whereas an opposite trend occurred for PTH. All parameters normalized after carbimazole therapy. Untreated hyperthyroid patients exhibited a significant elevation in serum ionized calcium and PTH-rP and a significant reduction in serum PTH levels when compared with healthy controls. Our data favoured the hypothesis of a direct involvement of PTH-rP in the pathogenesis of hypercalcemia in hyperthyroid patients.

The role of black seed and/ or bees honey in modulating the heart disorder induced by food additives in male rats.

Background: The present study aimed to throw the light on the potential hazards of some food additives whether preservatives such as sodium nitrite or colors as sunset yellow on the heart disorders through their own effect or the interaction between them. The study also, investigated the possible protective role of black seed and/ or bees honey against such risks. Results: Herein, the mentioned food additives caused significant elevations in serum and cardiac total lipids (TL), total cholesterol (TC), triglycerides (TG) and phospholipids (PL) levels as well as serum LDL-c, VLDL-c levels and LDL-c/HDL-c ratio. Meanwhile, significant decrements were shown in serum HDL-c level and HDL-c/TC ratio. Additionally, creatine kinase (CK) and aspartate transferase (AST) enzymes activity were increased significantly in serum and cardiac tissue. Moreover, oxidative stress markers; lipid peroxidation product (MDA) and protein carbonyl group (PC) were increased significantly in the cardiac tissue. Regarding, antioxidants; glutathione (GSH) content, glutathione -S -transferase (GST) and catalase (CAT) enzymes activity were decreased significantly in the cardiac tissue. Conclusion: However, the use of black seed and/ or bees honey ameliorated the disturbances observed indicating remarkable protection against the toxic effects of these food additives on the heart and offers more safety. Overall, here with the most pronounced effect was achieved by the combined treatment. In addition, the treatment by bees honey was more effective than black seed.

The role of black seed and/ or bees honey in modulating the heart disorder induced by food additives in male rats.

Background: The present study aimed to throw the light on the potential hazards of some food additives whether preservatives such as sodium nitrite or colors as sunset yellow on the heart disorders through their own effect or the interaction between them. The study also, investigated the possible protective role of black seed and/ or bees honey against such risks. Results: Herein, the mentioned food additives caused significant elevations in serum and cardiac total lipids (TL), total cholesterol (TC), triglycerides (TG) and phospholipids (PL) levels as well as serum LDL-c, VLDL-c levels and LDL-c/HDL-c ratio. Meanwhile, significant decrements were shown in serum HDL-c level and HDL-c/TC ratio. Additionally, creatine kinase (CK) and aspartate transferase (AST) enzymes activity were increased significantly in serum and cardiac tissue. Moreover, oxidative stress markers; lipid peroxidation product (MDA) and protein carbonyl group (PC) were increased significantly in the cardiac tissue. Regarding, antioxidants; glutathione (GSH) content, glutathione -S -transferase (GST) and catalase (CAT) enzymes activity were decreased significantly in the cardiac tissue. Conclusion: However, the use of black seed and/ or bees honey ameliorated the disturbances observed indicating remarkable protection against the toxic effects of these food additives on the heart and offers more safety. Overall, here with the most pronounced effect was achieved by the combined treatment. In addition, the treatment by bees honey was more effective than black seed.

Differences in postmortem urea nitrogen, creatinine and uric acid levels between blood and pericardial fluid in acute death

Previous studies showed significant differences in postmortem urea nitrogen (UN), creatinine (Cr) and uric acid (UA) levels in heart blood depending on the causes of death, including acute death. In addition, the levels in pericardial fluid approximated the clinical serum reference ranges, and their elevations may be assessed based on clinical criteria. The present study investigated difference between blood and pericardial levels of these markers. Medicolegal autopsy cases ( n = 556, within 48 h postmortem) of the following causes of death were examined: injury ( n = 136), asphyxiation ( n = 50), drowning ( n = 39), fire fatalities ( n = 99), hyperthermia ( n = 11), hypothermia ( n = 8), poisoning ( n = 26), delayed traumatic death ( n = 44) and natural diseases ( n = 143). When serum UN, Cr and UA levels were compared with the pericardial levels, there was an equivalency for delayed traumatic death and chronic renal failure, although each level was markedly elevated. Parallel increases in serum and pericardial UA and/or Cr levels were also observed for hypothermia and gastrointestinal bleeding. However, in drowning cases, the left cardiac and pericardial UN levels were lower than the right cardiac and peripheral levels, suggesting the influence of water aspiration. Significant elevations in serum and pericardial Cr and UA levels with a higher serum/pericardial UA ratio for fatal methamphetamine intoxication suggest progressive skeletal muscle damage due to advanced hypoxia/acidosis. Similar findings were often observed for other acute and subacute deaths. These findings suggest that a comparison between blood and pericardial nitrogenous compounds would be useful for investigating the cause and process of death.

Possible Roles of Fibroblast Growth Factor 23 in Developing X-Linked Hypophosphatemia

Fibroblast growth factor 23 (FGF23) was identified as a causative factor of autosomal dominant hypophosphatemic rickets (ADHR) and tumor-induced osteomalacia (TIO). Continuous administration of FGF23 by transplanting the FGF23-expressing CHO cells reproduced typical features observed in TIO patients, such as hypophosphatemia, low serum 1,25-dihydroxyvitamin D level, and osteomalacia in nude mice. A series of in vivo studies have shown that FGF23 can reduce sodium dependent phosphate co-transporter (NaPi2a) protein amount and 1α-hydroxylase mRNA level, and increase 24-hydroxylase mRNA levels in kidney. Fgf23 knockout mice demonstrated severe hyperphosphatemia, significant elevation in serum 1,25-dihydroxyvitamin D level and abnormal skeletal development. In addition, vitamin D treatment or dietary phosphate loading have been shown to stimulate FGF23 production. These evidences suggest that FGF23 plays an essential role in regulating phosphate and vitamin D metabolisms in normal physiology. On the other hand, the elevation of serum FGF23 levels in patients with X-linked hypophosphatemic rickets (XLH) has suggested important roles of FGF23 in developing XLH as well as ADHR and TIO. In our recent preliminary study, administration of anti-FGF23 neutralizing antibody ameliorated hypophosphatemia and rachitic bone characters in Hyp mice. These findings indicate a pathological contribution of FGF23 in development of XLH and may provide new insights to its therapy.

Immunogenicity of an Eight Amino Acid Domain Shared by Fas (CD95/Apo-I) and HIV-1 gp120. I. Structural and Antigenic Analysis

Previous studies have demonstrated that immunoglobulin G (IgG) antibodies to VEINCTR-N, a domain shared by Fas (CD95/Apo-I) and gp120, contribute to T-cell apoptosis during human immunodeficiency virus-type 1 (HIV-1) infection as a result of the agonist cross-linking of Fas. The present work was designed to determine whether these molecules are elicited primarily to HIV-1 or the cell receptor. Sera from 439 HIV-1-infected patients were screened by ELISA for their reactivity to VEINCTR-N. Subjects with significant serum elevations of IgG anti-VEINCTR-N were further investigated. Immunologic parameters, including CD4+ and CD8+ lymphocyte count, extent of T-cell apoptosis, occurrence of both anti-Fas antibodies and circulating soluble Fas titers, and reactivity to the 8-mer peptides resembling the flank-regions of VEINCTR-N on both gp120 V3 loop and Fas were examined. In addition, the antigenicity of these domains was assessed by biochemical and computerized analyses. 21 patients with significant levels of IgG to VEINCTR-N showed both an increased extent of peripheral T-cell apoptosis and binding to full-length Fas. A weak, though positive correlation of the anti-VEINCTR-N activity with its antecedent peptide on Fas was also found. Charge and structural analysis revealed that, although the extended 26-amino acid (a.a.) regions on both proteins were hydrophilic, the Fas peptide adjacent to VEINCTR-N expressed a short beta-conformed a.a. sequence in contiguity with a portion of the shared epitope, also in beta-sheet conformation. Patterns of antigenicity confirmed an apparent immunodominance of the full VEINCTR-N, based on its homology with the consensus sequence of other members of the tumor necrosis factor (TNF) receptor family. The hypothesis that the high immunogenicity of this region of Fas, rather than gp120, can drive the production of anti-VEINCTR-N antibodies also was supported by the concurrent significant elevations of soluble Fas in almost all of the sera studied. Our results indicate that a high release of the soluble form of Fas by T cells during the chronic immune activation of HIV-1 infection primes a humoral response against this epitope of Fas as a result of its high antigenicity. This is similar to the antibodies to tumor necrosis factor alpha (TNFalpha) receptor (R) (TNFalpha-R) that occur in response to increased levels of the soluble receptor for TNF during autoimmunity.

Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey

In our earlier study, we have observed that hypokalemia in langur monkeys, following gossypol acetic acid (GAA) treatment (5 mg dose level) when used as an antispermatogenic agent, and potassium salt supplementation partially maintained body potassium level of the animals. The aims of the present investigation was to confirm further occurrence of hypokalemia in the monkey (comparatively at two higher dose levels) and the role of potassium salt in preventing occurrence of gossypol-induced hypokalemia. Highly purified gossypol acetic acid alone at two dose levels (7.5 and 10 mg/animal/day; oral) and in combination with potassium chloride (0.50 and 0.75 mg/animal/day; oral) was given for 180 days. Treatment with gossypol alone as well as with the supplementation of potassium salt resulted in severe oligospermia and azoospermia. Animals receiving gossypol alone showed significant potassium deficiency with signs of fatigue at both dose levels. Enhanced potassium loss through urine was found in potassium-deficient animals, whereas animals receiving gossypol acetic acid plus potassium salt showed normal serum potassium with a less significant increase in urine potassium level during treatment phases. Other parameters of the body remained within normal range except gradual and significant elevation in serum transaminases activity. The animals gradually returned to normalcy following 150 and 180 days of termination of the treatment.

The effects of prednisolone and interferons on serum macrophage colony stimulating factor concentrations in chronic hepatitis B

Backgrounds/Aims: Serum concentrations of macrophage-colony stimulating factor (M-CSF) are increased in parallel with hepatic inflammation. The aim of this study was to assess the immunologic significance of elevated M-CSF in patients with chronic hepatitis B virus infection. Methods: The subjects included 20 asymptomatic HBV carriers and 45 patients with chronic hepatitis B, including 8 undergoing prednisolone treatment, 10 experiencing an acute exacerbation, and 12 undergoing daily administration of interferons. Results: Serum concentrations of M-CSF significantly decreased during prednisole administration, but significantly increased following prednisolone withdrawal, similar to the increase during acute exacerbation. Changes in the lipopolysaccharide-stimulated production of interleukin-1-beta and tumor necrosis factor-alpha by peripheral whole blood, or of interferon-gamma by peripheral blood mononuclear cells showed a similar pattern. Serum concentrations of M-CSF did not correlate with the titers of HBV-DNA or HBV-DNA polymerase activity. However, serum M-CSF peaked preceding seroconversion to HBe antibody in three HBe antigen positive patients. Exogenous interferon-alpha, -beta, or -gamma induced significant elevation in serum in M-CSF concentrations, irrespective of changes in the serum alanine aminotransferase levels. Conclusions: Increased serum M-CSF is closely associated with increased serum interfersons and/or proinflammatory cytokines produced by peripheral blood cells during hepatic inflammation in chronic hepatitis B. This may be a consequence of the altered cytokine cascade resulting from the host immune response against hepatitis B virus.

Potentiation of carbon tetrachloride hepatotoxicity by inhaled methanol: time course of injury and recovery.

Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. Because oral exposure to MeOH potentiates the hepatotoxicity of carbon tetrachloride (CCl4), we examined the ability of inhaled MeOH to potentiate CCl4 hepatotoxicity and the time course of injury and recovery. Adult male F-344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation for 6 h and gavaged with 0.075 ml CCl4/kg 24 h later. Hepatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30, and 61 d after CCl4 exposure. For CCl4 alone, hepatotoxicity was most severe at 0.5 and 1 d, when minimal centrilobular hepatocellular necrosis and predominately mild centrilobular hepatocellular vacuolar degeneration occurred. By d 3, the livers from the CCl4 rats were histologically normal. For MeOH+CCl4, peak severity of hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and moderate/marked centrilobular degeneration occurred. MeOH+CCl4 resulted in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased, relative to CCl4 alone, 171- and 113-fold, respectively, on d 1, and 166- and 140-fold, respectively, on d 1.5. Significant serum elevations in MeOH+CCl4 rats, relative to CCl4 alone rats, were present until d 7 and d 15 for AST and ALT, respectively. By d 3 and d 7, degeneration and necrosis, respectively, due to MeOH+CCl4 were essentially resolved. On d 7, the MeOH+CCl4 hepatic injury consisted mainly of chronic inflammation and centrilobular fibrosis. By d 30, the livers of MeOH+CCl4 rats were histologically normal. These data demonstrate that inhaled MeOH potentiates the hepatotoxicity of orally ingested CCl4, increasing the severity of CCl4 hepatotoxicity as well as the time required for recovery.