Pigment Deposition Research Articles

Utility of Scanning Electron Microscopy Elemental Analysis Using the 'NanoSuit' Correlative Light and Electron Microscopy Method in the Diagnosis of Lanthanum Phosphate Deposition in the Esophagogastroduodenal Mucosa.

Background: We have recently developed the correlative light and electron microscopy of hematoxylin and eosin (H&E)-stained glass slides using the ‘NanoSuit’ method. The aim of this study is to explore the utility of the new NanoSuit-correlative light and electron microscopy method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy elemental analysis for the diagnosis of lanthanum phosphate deposition in the H&E-stained glass slides. Methods: Nine H&E-stained glass slides of the upper gastrointestinal tract mucosa containing the brown pigmented areas by light microscopic observation, which were suspected as lanthanum phosphate deposition, were observed and analyzed by scanning electron microscopy-energy dispersive X-ray spectroscopy using the NanoSuit-correlative light and electron microscopy method. Results: In all nine slides, the new NanoSuit-correlative light and electron microscopy method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy revealed the accumulation of both lanthanum and phosphorus in the tissue area corresponding to the brown pigment deposition. In addition to the existence of lanthanum phosphate in the stomach and duodenum, known target organs, we observed deposition in the esophagus for the first time. Furthermore, we observed lanthanum phosphate deposition in the background mucosa of stomach containing primary adenocarcinoma. Conclusions: Scanning electron microscopy-energy dispersive X-ray spectroscopy analysis using the NanoSuit-correlative light and electron microscopy method is useful for the diagnosis of lanthanum phosphate deposition in the H&E-stained glass slides. Lanthanum phosphate deposition occurs not only in the stomach and duodenum but also in the esophagus.

A large-scale collection of giant congenital melanocytic nevi: Clinical and histopathological characteristics.

Giant congenital melanocytic nevi (GCMN) place a heavy psychological burden on patients due to their poor cosmetic appearance. The histopathological characteristics of GCMN have remained largely elusive. The present study investigated the histopathological characteristics of GCMN in association with their clinical appearance. A total of 98 patients diagnosed with GCMN were included in the present study and their clinical features were collected from their records. Lesion specimens were obtained and stained for histopathological analysis. Regarding the microscopic appearance of GCMN, nevi cells in the whole dermis exhibited different patterns than those in healthy tissues. Most GCMN cases featured a sub-epidermal non-involvement zone, which implies an early occurrence in embryo development. Darker nevi exhibited a higher density of infiltrated nevi cells and more pigment deposition; this appears to induce a poor skin texture. Chemical peeling and laser therapy only partly removes pigment particles and nevi cells in the upper portion of the dermis. The clinical features of GCMN are associated with the histopathological characteristics, and non-surgical therapy cannot remove the nevus cells in the deep dermis.

Spontaneous Rupture of Spleen in a Malaria Patient- A Case Report

Spontaneous splenic rupture is a life threatening complication of malaria. Splenectomy has been recommended as the treatment option for hemodynamically unstable patients. Herein, we report a 29-year-old gentleman presented with high grade fever, acute abdomen and vomiting for three days. Laboratory evaluation did not show malaria parasite on the peripheral film. A CT abdomen done outside showed splenomegaly and hemoperitoneum. The patient deteriorated and underwent emergent exploratory laparotomy. Splenectomy was performed and large clots were evacuated. The subsequent biopsy of the ruptured spleen showed marked hemorrhagic necrosis and hemozoin pigment deposits consistent with malaria sequestered spleen. Detection of such a complication requires a high index of clinical suspicion and is extremely challenging in a patient with MP negative on peripheral film.

3119 Pseudomelanosis of Stomach and Duodenum

INTRODUCTION: Pigmentation of the lower gastrointestinal tract called melanosis coli is a commonly encountered endoscopic finding. A similar pattern of pigmentation called pseudomelanosis is sometimes encountered during upper GI endoscopies. Duodenum is the most commonly reported site for pseudomelanosis, but there have been limited number of reported cases of gastric pseudomelanosis. CASE DESCRIPTION/METHODS: We present a case of 71 year old male with history of iron deficiency anemia, coronary artery disease, congestive heart failure, chronic kidney disease, hypertension, gout and hyperlipidemia who presented for GI endoscopy to evaluate his anemia. His medications included torsemide, hydralazine, ferrous sulfate, clopidogrel, pantoprazole, febuxostat, atorvastatin, amlodipine, isosorbide mononitrate, bisoprolol, irbesartan, citalopram, doxazosin and oxybutynin. Esophagogastroduodenoscopy (EGD) revealed a 3 mm dark spot in the antrum which was biopsied (Figure 1). Similar pigmentation was seen in the duodenum as well (Figure 2). Pathology revealed benign gastric mucosa with histological pattern of pseudomelanosis. Rest of the gastric mucosa was benign with non-specific chronic inflammation. Additional endoscopic findings observed were a linear pattern of mild erythema in the gastric antrum which was consistent with endoscopic appearance of gastric antral vascular ectasia. No active bleeding or oozing was observed. Rest of the EGD, as well as colonoscopy was unremarkable except for multiple small colon polyps. DISCUSSION: The exact etiopathogenesis of this rare entity remains unclear and various mechanisms have been proposed for this pigmentation pattern. Iron supplementation or upper GI bleeding leading to abnormal iron accumulation in macrophages of lamina propria has been proposed as a possible mechanism. Results of electron probe X-ray identified the role of sulfur containing compounds in causing accumulation of this pigment. Conditions associated with pseudomelanosis are CKD, hypertension, gastric hemorrhage and diabetes. Medications such hydralazine, thiazide, furosemide, Iron sulfate, methyldopa and propranolol have been shown to be associated with it. Sulfur containing drugs (such as hydralazine, furosemide and hydrochlorothiazide) are worth mentioning, since sulfur is shown to promote pigment deposition. The clinical significance, treatment and follow up of this rare condition is still unknown. Furthermore, no malignant transformation or long term complications have been reported so far.

3215 Duodenal Blackout: A Rare, Benign Endoscopic Finding

INTRODUCTION: First described in 1976, psuedomelanosis is a rare, benign, incidental endoscopic finding most commonly seen in the duodenum. PD has been associated with chronic renal disease and the ingestion of various medications including hydralazine and iron supplements. Here we describe a classic presentation of an uncommon endoscopic abnormality. CASE DESCRIPTION/METHODS: A 66-year-old woman with decompensated cirrhosis, end stage renal disease, and hypertension presented to the hospital with hepatic encephalopathy and failure to thrive. Her medications included hydralazine and a history of iron supplementation. An esophagogastroduodenoscopy (EGD) performed for early satiety, weight loss and to initiate a liver transplant evaluation demonstrated diffuse mucosal hyperpigmentation in a striped pattern, predominantly in the second portion of the duodenum (Figure 1). Mucosal biopsy revealed an abundance of brown pigment deposition in the lamina propria (Figure 2) which was negative on Prussian blue stain and immunohistochemistry—consistent with a diagnosis of pseudomelanosis duodeni (PD). DISCUSSION: Despite its striking endoscopic appearance, there is no evidence that pseudomelanosis duodeni is associated with any progressive pathology. Though PD has been described anecdotally in case report and case series, little is known about the pathophysiology. Some have posited PD is related to iron or lipofuscin deposition in the lamina propria. PD has been associated with end-stage renal disease, hydralazine, thiazide diuretics, and iron supplementation. This case describes a classic presentation of PD with the archetypal imaging and histopathology to support the diagnosis of this uncommon condition.

2720 Iron Pill-Induced Gastropathy in Elderly Patients: A Case Series Report

INTRODUCTION: Iron deficiency anemia is a global health problem with an estimated two billion cases worldwide. Oral iron supplementation is considered the first line treatment. However, recent studies favor the use of short-term IV iron especially in patients with drug tolerance and efficacy concerns. In this report, we present three cases of iron pill gastropathy in patient's whose clinical courses were complicated by gastric erosion, ulcer or gastrointestinal (GI) bleeding. All of our patients had a history of iron deficiency anemia and were being treated with oral ferrous sulfate. CASE DESCRIPTION/METHODS: The first case involved a 72-year-old male with multiple comorbidities was admitted to the hospital for an NSTEMI. Initial labs revealed severe microcytic anemia (Table 1). He denied any hematemesis, melena, or hematochezia. During his hospital stay, he underwent an EGD which showed several erosions in the antrum with no active hemorrhage or visible vessels. Biopsy taken from the erosions demonstrated reactive gastritis with chronic inflammation and focal pigmented deposits stained positive with iron dye. After establishing the diagnosis iron gastropathy, the patient was transitioned to IV iron. In a second case, an 81-year-old male presented with a three-day history of abdominal pain associated with nausea and vomiting. The patient was started on proton pump inhibitors, IV hydration, and antiemetics for suspected acute gastritis with complete resolution of the symptoms. Severe anemia on initial labs prompted an EGD, which showed a superficial ulcer in the gastric body with a caustic appearance. Microscopically, focal iron deposits were remarkable in the area of erosions and were consistent with iron gastritis. Lastly, an over-90-year-old female presented with acute shortness of breath. Initial labs revealed worsening iron deficiency anemia. An EGD showed erosions within the gastric body with mild superficial gastritis. Microscopically, biopsied erosions showed yellow deposits within the mucosa, which stained positive for iron. DISCUSSION: Iron pill gastropathy is an underrecognized condition particularly in the elderly. The liquid form of oral iron has been shown to be less toxic to the gastric mucosa compared to the tab formulation. Transition to liquid or IV iron should be considered in patients with iron gastropathy as use of iron pills can lead to gastric erosions, ulcers, and GI bleeding, which can worsen the underlying anemia and result in cardiovascular symptoms related to severe anemia.

Clinical, ultrasonographic, and histopathologic findings in seven horses with Descemet's membrane detachment: A case series

ObjectiveTo describe ultrasonography as a diagnostic method of in vivo Descemet's membrane detachment (DMD) in horses. Animals studied: Seven horses (three Icelandic horses, two Dutch Warmblood horses, one Appaloosa, and one Welsh Pony), presenting with moderate‐to‐severe focal or diffuse corneal edema, in whom DMD was suspected on ultrasonographic examination and confirmed with histopathology, were studied.ProcedureA retrospective analysis of case records of horses with suspected DMD was performed.ResultsMedian age at presentation was 14 years (range 11‐24). Clinical signs in eyes with DMD were unilateral in all horses and included blepharospasm and epiphora (6/7), buphthalmos (5/7), moderate‐to‐severe focal or diffuse corneal edema (7/7), corneal epithelial bullae (4/7), corneal neovascularization (4/7), Haab's striae (2/7), corneal endothelial precipitates (1/7), fibrin in the anterior chamber (1/7), focal cataract (2/7), and pigment deposits on the anterior lens capsule (1/7). During transpalpebral ultrasonography, a distinct linear echogenic structure was noted in the anterior chamber, initially diverging from, and later running parallel to, the posterior lining of the cornea in all eyes studied. In all cases, the cornea was severely thickened and echogenic, consistent with edema, and DMD was suspected. In all horses, the clinical signs progressed and the affected eye was eventually enucleated. Histopathology revealed DMD (7/7), spindle cell proliferation (4/7), Descemet's membrane reformation (3/7), and inflammation of the anterior uvea (5/7). Overall incidence was 1.04%.ConclusionsUltrasonography is an adequate tool in diagnosing DMD in horses. Descemet's membrane detachment should be included in the differential diagnosis in horses with dense focal or diffuse corneal edema.

Fasciolosis: grading the histopathological lesions in naturally infected bovine liver in Mosul city

Fasciolosis cause economic losses in cattle that breed in Iraq and the world. About 4% of bovine liver’s samples included in the current study exhibited classical pathological lesions of fasciolosis. Samples of cattle livers infected with fasciolosis were taken for histopathology. Eighteen grading criteria with four scoring level have been chosen to grading the microscopic lesions caused by Fasciola hepatica into a mild infection (grade I), moderate infection (grade II) and severe infection (grade III). The type of hepatic degeneration or necrosis, cloudy cell swelling, coagulative necrosis, infiltration of inflammatory cells, with patterns of infiltration, also type of infiltrated cells, fibrosis between hepatic cells or in portal area, affection to hepatic cords arrangement, hepatic sinusoids, extensions of hemorrhage, pigment deposition, hyperplasia of bile duct, thickness of hepatic capsule and presence of liver fluke were the main grading levels. In grade, I the microscopic lesions were characterized by simple or mild in their nature with very good reversible prognosis, while grade II characterized by moderate severity of the lesions with a good reversible prognosis, while grade III characterized by hostile severity with bad irreversible prognosis as a result of architecture changes in liver histology. In conclusion, we believed that this grading system could be used as a guide when examining histopathological liver's samples infected with F. hepatica to identify the stage of infection and proposed an accurate prognosis.

In Vivo Hepato-Nephroprotective Role of Nigella sativa Seed Extract Against Lead Nitrate [Pb(NO3)2] Induced Toxicity in Albino Mice

In this study, toxic effects of lead nitrate [Pb(NO3)2] and the hepato-nephroprotective role of Nigella sativa seed extract (NSSE) against toxicity were studied in albino mice. For this aim, mice were randomly divided into six groups as: Group I treated with tap water, Group II: 300 mg kg-1 bw NSSE, Group III: 600 mg kg-1 bw NSSE, Group IV: 500 mg kg-1 bw Pb(NO3)2, Group V: 300 mg kg-1 bw NSSE+500 mg kg-1 bw Pb(NO3)2, Group VI: 600 mg kg-1 bw NSSE+500 mg kg-1 bw Pb(NO3)2. After experimental procedure the changes in blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT), aspartate transaminase (AST) levels of blood serum, glutathione (GSH) and malondialdehyde (MDA) levels of liver and kidney tissues were investigated. And also histopathological examinations of liver and kidney tissues were studied. At result, significant increases were observed in BUN, creatinine, ALT, AST levels of mice treated with Pb(NO3)2. GSH levels were decreased, MDA levels were increased in kidney and liver tissues after Pb(NO3)2 treatment. In histopathological examinations binucleated cell, karyomegaly, stellate cell and bilirubin pigment deposit were observed in liver tissue while hyaline cast, thickening of the basement membrane, albumonid content and inflammatory leukocytes were observed in kidney tissue in Group IV. NSSE treatment in Group V and VI was ameliorated the toxic changes in level of serum parameters, GSH and MDA levels and histopathological damages of tested tissues. As a result, it was determined that NSSE decreases hepato-nephrotoxicity with a dose dependent manner induced by Pb(NO3)2 and leads to an improvement associated with its components.

PD-L1 expression in gastric cancer determined by digital image analyses: pitfalls and correlation with pathologist interpretation

Programmed death ligand-1 (PD-L1) immunohistochemistry is used to predict response to anti-PD-L1 therapy. However, intra- and inter-observer variability influence the prediction of PD-L1 expression. Unlike evaluations of non-small cell lung cancer according to PD-L1 expression determined by tumor proportion score, gastric cancer is evaluated using combined positive scores. We aimed to compare the results of digital image analysis and pathologists' interpretations for predicting response to pembrolizumab in gastric cancer patients. Gastric cancer tissues from patients enrolled in a clinical trial of pembrolizumab were reviewed, and 39 cases were analyzed. PD-L1 22C3 PharmDx (Dako) immunohistochemistry slides were interpreted by digital image analysis and by the consensus of two pathologists, and the results of interpretations were compared with the eventual clinical responses to pembrolizumab. In direct comparisons of digital image analyses and pathologists' interpretations, 33 (84.6%) out of 39 cases showed concordant results. In 6 (15.4%) cases, weak staining of PD-L1, anthracotic pigment deposits, or decalcification artifacts caused discordant results, and all the cases were challenging. In statistical analyses, PD-L1 expression as interpreted by pathologists and digital image analysis did not differ significantly for predicting responses to pembrolizumab (P = 0.1856). Digital image analyses and pathologists' interpretations showed concordant results for PD-L1 combined positive scores in most cases, and the prediction performances of each were not significantly different.

Distribution of nickel and chromium containing particles from tattoo needle wear in humans and its possible impact on allergic reactions

BackgroundAllergic reactions to tattoos are amongst the most common side effects occurring with this permanent deposition of pigments into the dermal skin layer. The characterization of such pigments and their distribution has been investigated in recent decades. The health impact of tattoo equipment on the extensive number of people with inked skin has been the focus of neither research nor medical diagnostics. Although tattoo needles contain high amounts of sensitizing elements like nickel (Ni) and chromium (Cr), their influence on metal deposition in skin has never been investigated.ResultsHere, we report the deposition of nano- and micrometer sized tattoo needle wear particles in human skin that translocate to lymph nodes. Usually tattoo needles contain nickel (6–8%) and chromium (15–20%) both of which prompt a high rate of sensitization in the general population. As verified in pig skin, wear significantly increased upon tattooing with the suspected abrasive titanium dioxide white when compared to carbon black pigment. Additionally, scanning electron microscopy of the tattoo needle revealed a high wear after tattooing with ink containing titanium dioxide. The investigation of a skin biopsy obtained from a nickel sensitized patient with type IV allergy toward a tattoo showed both wear particles and iron pigments contaminated with nickel.ConclusionPreviously, the virtually inevitable nickel contamination of iron pigments was suspected to be responsible for nickel-driven tattoo allergies. The evidence from our study clearly points to an additional entry of nickel to both skin and lymph nodes originating from tattoo needle wear with an as yet to be assessed impact on tattoo allergy formation and systemic sensitization.

Comprehensive Clinical, Diagnostic, and Advanced Imaging Characterization of the Ocular Surface in Spontaneous Aqueous Deficient Dry Eye Disease in Dogs.

To perform a comprehensive clinical, diagnostic, and imaging characterization of the ocular surface in West Highland White Terriers (WHWTs) diagnosed with aqueous deficient dry eye (ADDE) disease. Six ADDE-affected and 13 ADDE-unaffected WHWT dogs were enrolled and underwent clinical assessment and disease scoring, tear osmolarity, phenol red thread test, Schirmer tear test, tear film breakup time, fluorescein staining, Rose bengal and lissamine green vital dye staining, meibometry, corneal esthesiometry, ultrasound pachymetry, optical coherence tomography, in vivo confocal microscopy, and conjunctival biopsy. Subjective assessment of their condition was provided by owner-reported surveys. ADDE-affected WHWT dogs had higher median clinical disease (conjunctiva: 5.75 vs. 0.00; cornea: 14.00 vs. 5.00; total: 17.50 vs. 5.00), vital staining (Rose bengal: 2.25 vs. 1.50; lissamine green: 2.00 vs. 1.00), and histologic disease (conjunctiva: 2 vs. 0) scores when compared with the controls. In addition, ADDE-affected WHWTs had significantly lower phenol red thread test (5.0 vs. 17.5, mm/15 s), Schirmer tear test (3 vs. 20, mm/min), tear film breakup time (3.6 vs. 13.9, s) values and higher area under the curve values for meibometry (394 vs. 245, meibometry units [MU]). There were no significant differences in other tear film tests performed. Advanced imaging revealed decreased tear meniscus height (optical coherence tomography) and variable pigment deposition within corneal epithelial cells (in vivo confocal microscopy). This comprehensive assessment of ADDE-affected WHWTs depicts the ocular surface changes associated with quantitative lacrimal gland dysfunction. Importantly, ADDE-affected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.

Diagnosis of Retinitis Pigmentosa from Retinal Images

Retinitis pigmentosa is a genetic disorder that results in nyctalopia and its progression leads to complete loss of vision. The analysis and the study of retinal images are necessary, so as to help ophthalmologist in early detection of the retinitis pigmentosa . In this paper fundus images and Optical Coherence Tomography images are comprehensively analyzed , so as to obtain the various morphological features that characterize the retinitis pigmentosa . Pigment Deposits, important trait of RP is investigated. Degree of darkness and entropy are the features used for analysis of PD. The darkness and entropy of the PD is compared with the different regions of the fundus image which is used to detect the pigments in the retinal image. Also the performance of the proposed algorithm is evaluated by using various performance metrics. The performance metrics are calculated for all 120 images of RIPS dataset. The performance metrics such as sensitivity, sensibility, specificity, accuracy, F-score, equal error rate, conformity coefficient, Jaccard's coefficient, dice coefficient, universal quality index were calculated as 0.72, 0.96, 0.97, 0.62, 0.12, 0.09, 0.59, 0.45 and 0.62, respectively.

Expression of glucocorticoid and mineralocorticoid receptor genes co-varies with a stress-related colour signal in barn owls

Glucocorticoid hormones are important intermediates between an organism and its environment. They enable an organism to adjust its behavioural and physiological processes in response to environmental changes by binding to mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) expressed in many tissues, including the integument. The regulation of glucocorticoids co-varies with melanin-based colouration in numerous species, an association that might result from pleiotropic effects of genes in the melanocortin system and evolve within a signalling context. Most studies have focused on the circulating levels of glucocorticoids disregarding the receptors that mediate their action, and that might partly account for the covariation between the regulation of stress and melanin-based colouration. We investigated the association of the expression levels of GR and MR genes with melanin-based colouration in the growing feathers of nestling barn owls (Tyto alba). We also explored the association between GR and MR expression levels and the expression of genes related to the melanocortin system and melanogenesis to better understand the origin of the link between the expression of receptors to which corticosterone binds and melanin-based colouration. Nestling barn owls displaying larger eumelanic black feather spots expressed GR and MR at lower levels than smaller-spotted individuals. However, we found that the expression of the GR and MR genes was positively rather than negatively correlated with the expression of genes involved in the deposition of melanin pigments at the time we sampled the nestlings. This provides mixed evidence of the association between melanin-based traits and MR and GR gene expression. The finding that the expression of GR and MR was positively associated with the expression of the PCSK2 gene (encoding one of the protein convertase responsible for the production of hormone peptide ACTH and α-MSH) suggests that the melanocortin system may be implicated in the establishment of the covariation between melanin-based colour and the expression of receptors to which glucocorticoids bind. However, further studies investigating the expression of melanin-based traits with stress-related endpoints at different time points of feather development will be necessary to understand better the proximate mechanism linking melanin-based traits with stress.

Fuchs endothelial corneal dystrophy and corneal endothelial diseases: East meets West.

Fuchs endothelial corneal dystrophy (FECD) is amongst one of the most common indications for endothelial keratoplasty worldwide. Despite being originally described among Caucasians, it is now known to be prevalent among a large number of populations, including Asians. While the FECD phenotype is classically described as that of central guttate and pigment deposits associated with corneal endothelial dysfunction, there are subtle yet important differences in how FECD and its phenocopies may present in Caucasians vs Asians. Such differences are paralled by genotypic variations and disease management preferences which appear to be geographically and ethnically delineated. This article provides a succinct review of such differences, with a focus on diagnostic and management issues which may be encountered by ophthalmologists practicing in the different geographic regions, when evaluating a patient with FECD.

Pollution induced change of liver of Oreochromis niloticus: metals accumulation and histopathological response

The present study, pointed to assess heavy metal accumulation like Aluminum (Al), Cadmium (Cd), Chrome (Cr), Cobalt(Co), Copper(Cu), Iron(Fe), Lead (Pb), Manganese(Mn), Nickel(Ni), Selenium(Se) and Zinc(Zn) in water, sediments and liver of Oreochromis niloticus, which collected from sewage water in El-kharja, New Valley, Egypt using inductively coupled plasma mass spectrometry (ICP-MS). Also, the histopathological changes of liver of Oreochromis niloticus were reported. These histopathological changes were detected using different staining types as a pollution biomarker. Iron showed the highest accumulation level in water (9.06±0.86 ppm), sediments (175.1±20.8 ppm) and liver (158.17±38.59 ppm), followed by Al> Mn> Ni> Zn> Pb> Cr> Se> Cu> Co> Cd. However, these elements showed Fe> Al> Ni> Mn> Cr> Cu> Zn> Pb> Cd> Se> Co accumulation trend in sediments. In liver these metals showed Fe> Se>Al> Zn>Mn> Cu>Ni> Cr> Pb> Co> Cd trend. Histopathological examination of fish liver showed signs of progressive alterations such as disorganization of architecture of liver cells, hydropic degeneration and vacuolation of hepatocytes. Also, dilation and congestion in blood sinusoids, hypertrophic and increase in number of küpffer cells were chronicled. Sever deposition of hemosiderin pigments were reported while necrosis with pyknotic nucleus and focal histopathological characters were observed side by side with normal cell. Our results concluded that water, sediment and liver accumulation toxicity tests and histopathological changes of liver may be associated, and these approaches may be used together to describe the environmental state and water quality assessment.

Effect of vitamin D on the spleen of adult male rats fed on diet with high fat: A histological and immunohistochemical study.

Background: High fat diet (HFD) is the cause of obesity prevalence which is a serious health problem. Vitamin D is considered a very important modulator in cellular inflammation and immune systems.Aim of the work: To demonstrate the histological changes in the spleen of the adult male rats fed with HFD and to evaluate vitamin D role in counteracting the harmful effects of HFD on the spleen.Materials and Methods: A total number of 36 male adult albino rats which were classified equally and randomly into three groups as follows; Control group where rats were administered the control diet for a period of 10 weeks, HFD fed group which was administered HFD for 10 weeks and HFD + vitamin D group which was administered HFD concomitantly with vitamin D orally daily for 10 weeks at a dose of 1 ug (40 IU)/kg. Samples from the spleen were prepared for histological and immunohistochemical study.Results: The group received HFD revealed marked histological alterations with lymphatic follicles proliferation. Most splenic cells showed degenerative changes. Deposition of hemosidrin pigments, markedly dilated blood sinusoids and blood extravasation were observed. CD86 had a strong cytoplasmic expression in dendritic cells. Moreover, cytoplasmic immune reaction for iNOS and caspase-3 in the white and red pulps of the spleen was intense. Vitamin D co-adminstration greatly preserved the histological and immunohistochemical structure of the spleen.Conclusion: This study suggests that vitamin D has a role in splenic protection and can attenuate the deleterious effects commonly detected in the spleen and immune system in case of obesity induced by HFD.

Whole-exome sequencing identifies novel mutations in genes responsible for retinitis pigmentosa in 2 nonconsanguineous Chinese families.

To detect the pathogenetic mutations responsible for nonsyndromic autosomal recessive retinitis pigmentosa (RP) in 2 nonconsanguineous Chinese families. The clinical data, including detailed medical history, best corrected visual acuity (BCVA), slit-lamp biomicroscope examination, fundus photography, optical coherence tomography, static perimetry, and full field electroretinogram, were collected from the members of 2 nonconsanguineous Chinese families preliminarily diagnosed with RP. Genomic DNA was extracted from the probands and other available family members; whole-exome sequencing was conducted with the DNA samples provided by the probands, and all mutations detected by whole-exome sequencing were verified using Sanger sequencing in the probands and the other available family members. The verified novel mutations were further sequenced in 192 ethnicity matched healthy controls. The patients from the 2 families exhibited the typical symptoms of RP, including night blindness and progressive constriction of the visual field, and the fundus examinations showed attenuated retinal arterioles, peripheral bone spicule pigment deposits, and waxy optic discs. Whole-exome sequencing revealed a novel nonsense mutation in FAM161A (c.943A>T, p.Lys315*) and compound heterozygous mutations in RP1L1 (c.56C>A, p.Pro19His; c.5470C>T, p.Gln1824*). The nonsense c.5470C>T, p.Gln1824* mutation was novel. All mutations were verified by Sanger sequencing. The mutation p.Lys315* in FAM161A co-segregated with the phenotype, and all the nonsense mutations were absent from the ethnicity matched healthy controls and all available databases. We identify 2 novel mutations in genes responsible for autosomal recessive RP, and the mutation in FAM161A is reported for the first time in a Chinese population. Our result not only enriches the knowledge of the mutation frequency and spectrum in the genes responsible for nonsyndromic RP but also provides a new target for future gene therapy.

Bilateral acute iris transillumination (BAIT) syndrome: literature review.

The authors conducted a literature review about bilateral acute iris transillumination (BAIT) syndrome, a new and relatively unknown syndrome that should be described and made known to the greatest number to avoid potential diagnostic and therapeutic errors. The first cases date back only to 2004 and a total of 79 cases have been published to date, mainly in Europe and especially in Turkey and Belgium. It mainly affects young women between the ages of 30 and 50, and symptoms are often preceded by an upper airway infection. There is also a majority of cases where the onset of the syndrome follows oral intake of moxyfloxacin. The clinical signs are dominated by strong photophobia, secondary to a spectacular transillumination of the iris. Other classical symptoms are conjunctival infection, eye pain, blurred vision, temporary ocular hypertonia, fixed mid-dilated pupils, and pigment dispersion in the anterior chamber with pigmentary deposits in the trabecular meshwork in gonioscopy, symptoms that may be mistaken for uveitis. After a few weeks or months of evolution, persistent sequelae were pupillary atony and chronic and bilateral transillumination of the iris, leading to significant photophobia and sometimes persistent ocular hypertension. The BAIT syndrome is close to the bilateral acute depigmentation of the iris (BADI) syndrome, which is similar to BAIT but lacks associated transillumination. A few cases of patients with BAIT syndrome on one eye and BADI syndrome on the contralateral eye have been described, which confirms some form of link between the two clinical entities.

Molecular characterization of foveal versus peripheral human retina by single-cell RNA sequencing

The human retina is a complex tissue responsible for detecting photons of light and converting information from these photons into the neurochemical signals interpreted as vision. Such visual signaling not only requires sophisticated interactions between multiple classes of neurons, but also spatially-dependent molecular specialization of individual cell types. In this study, we performed single-cell RNA sequencing on neural retina isolated from both the fovea and peripheral retina in three human donors. We recovered a total of 8,217 cells, with 3,578 cells originating from the fovea and 4,639 cells originating from the periphery. Expression profiles for all major retinal cell types were compiled, and differential expression analysis was performed between cells of foveal versus peripheral origin. Globally, mRNA for the serum iron binding protein transferrin (TF), which has been associated with age-related macular degeneration pathogenesis, was enriched in peripheral samples. Cone photoreceptor cells were of particular interest and formed two predominant clusters based on gene expression. One cone cluster had 96% of cells originating from foveal samples, while the second cone cluster consisted exclusively of peripherally isolated cells. A total of 148 genes were differentially expressed between cones from the fovea versus periphery. Interestingly, peripheral cones were enriched for the gene encoding Beta-Carotene Oxygenase 2 (BCO2). A relative deficiency of this enzyme may account for the accumulation of carotenoids responsible for yellow pigment deposition within the macula. Overall, this data set provides rich expression profiles of the major human retinal cell types and highlights transcriptomic features that distinguish foveal and peripheral cells.