A rare cutaneous infection with Mycobacterium chelonae in a pediatric patient treated with trametinib for KRAS-mutated diffuse glioma.

Mitogen-activated extracellular signal-regulated kinase inhibitors (MEKi) represent a promising new therapy for pediatric patients with low-grade gliomas, which frequently have abnormal signaling within the mitogen-activated protein kinase (MAP kinase) pathway. However, understanding of long-term efficacy and toxicity is limited in pediatric glioma patients. This article describes a rare presentation of a widespread cutaneous infection with Mycobacterium chelonae in a pediatric patient with a low-grade glioma treated with trametinib.

Disseminated Histoplasmosis presenting as oropharyngeal mass lesion.

A 62 year old man from Silchar in North East India presented with complaints of painful swallowing, hoarseness, fever, anorexia and weight loss. Oropharyngeal examination revealed reddish ulcero-nodular lesion involving left tonsillar area and base of tongue which was clinically suspicious of malignancy. Radiological examination revealed involvement of bilateral adrenals by a mass. The biopsy of the oropharyngeal lesion showed many fungal spores morphologically favoring Histoplasmosis. Treatment with Amphotericin B followed by Itraconazole resulted recovery of lesions.

Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice.

BACKGROUND: Salidroside, an active component from Traditional Chinese Medicine Rhodiola rosea L., has various pharmacological functions including anti-inflammatory, anti-cancer and anti-oxidative properties. However, whether salidroside plays a beneficial role in diabetic nephropathy is still unclear. PURPOSE: The objective of this work was to investigate the potential roles of salidroside against diabetic nephropathy and the underlying molecular mechanisms. METHODS: Streptozocin was given to obese mice to generate diabetic nephropathy animal model. Salidroside was administered to these mice and proteinuria, podocyte integrity, renal morphology and fibrosis, mitochondrial biogenesis were examined. RESULTS: Our results showed that salidroside treatment greatly attenuates diabetic nephropathy as evidenced by decreased urinary albumin, blood urea nitrogen and serum creatinine. Morphological analysis indicated that salidroside improves renal structures in diabetic nephropathy. The decreases in nephrin and podocin expression were markedly reversed by salidroside. Moreover, kidney fibrosis in diabetic nephropathy mice was largely prevented by salidroside. Mechanistically, in salidroside-treated mice, the mitochondrial DNA copy and electron transport chain proteins were significantly enhanced. Meanwhile, the reduced Sirt1 and PGC-1α expression in diabetic nephropathy was almost completely counteracted in the presence of salidroside. CONCLUSIONS: Our data showed that salidroside plays a beneficial role against diabetic nephropathy in mice, which probably via Sirt1/PGC-1α mediated mitochondrial biogenesis.

TRPC6 inactivation does not affect loss of renal function in nephrotoxic serum glomerulonephritis in rats, but reduces severity of glomerular lesions.

Canonical transient receptor potential-6 (TRPC6) channels have been implicated in a variety of chronic kidney diseases including familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) and renal fibrosis following ureteral obstruction. Here we have examined the role of TRPC6 in progression of inflammation and fibrosis in the nephrotoxic serum (NTS) model of crescentic glomerulonephritis. This was assessed in rats with non-functional TRPC6 channels due to genomic disruption of an essential domain in TRPC6 channels (Trpc6 del/del rats) and wild-type littermates (Trpc6 wt/wt rats). Administration of NTS evoked albuminuria and proteinuria observed 4 and 28 days later that was equally severe in Trpc6 wt/wt and Trpc6 del/del rats. By 28 days, there were dense deposits of complement and IgG within glomeruli in both genotypes, accompanied by severe inflammation and fibrosis readily observed by standard histological methods, and also by increases in renal cortical expression of multiple markers (α-smooth muscle actin, vimentin, NLRP3, and CD68). Tubulointerstitial fibrosis appeared equally severe in Trpc6 wt/wt and Trpc6 del/del rats. TRPC6 inactivation did not protect against the substantial declines in renal function (increases in blood urea nitrogen, serum creatinine and kidney:body weight ratio) in NTS-treated animals, and increases in a urine maker of proximal tubule pathology (ß2-macroglobulin) were actually more severe in Trpc6 del/del animals. By contrast, glomerular pathology, blindly scored from histology, and from renal cortical expression of podocin suggested a partial but significant protective effect of TRPC6 inactivation within the glomerular compartment, at least during the autologous phase of the NTS model.

Cytological and histological correlation of granular cell tumor in a series of three cases.

Granular cell tumor (GCT) is an uncommon soft tissue tumor characterized by proliferation of cells with granular eosinophilic cytoplasm. We came across three such tumors, one in the tongue, one in the chest wall, and one in the right deltoid region, which were referred for fine-needle aspiration cytology. On cytological examination, the first two cases were diagnosed as GCT, and the mass in deltoid region was suggestive of proliferative myositis. The cytological details of these cases are discussed. The excision biopsies of the first two cases and Tru-cut biopsy of the deltoid mass confirmed the diagnosis of GCT.

Periodic acid-Schiff (PAS) reaction and plastination in whole body slices. A novel technique to identify fascial tissue structures.

Since collagen rich fascial tissue is often very delicate and difficult to discern on native tissue slices, we have developed a method for staining full-body slices using the periodic acid-Schiff (PAS) reaction with subsequent plastination. Since the PAS reaction primarily stains carbohydrates, we could exploit the circumstance that different collagen types vary in carbohydrate content. Contrary to fasciae, tissues such as muscle, bone, nerves and blood vessels exhibit significantly less staining or remain unstained. We have validated the whole-body slice staining results in microscopic tissue slides which were stained with standard extracellular matrix stains such as Masson-Goldner trichrome stain and van-Gieson stain. Furthermore, we have performed immunofluorescence imaging to confirm the presence of collagen in the stained tissue. We achieved very good staining and plastination results and were able to clearly identify even very thin fascia in transversal body slices. This technique may prove useful in advancing our knowledge on the complex topography of fascial structures.

Study of the effects of cyclooxygenase-2 inhibitor on the promotion of hepatic tumorigenesis in rats fed a high fat diet.

BACKGROUND/OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The highest prevalence of hepatitis is an important risk factor contributing to development of HCCs. However, an increasing number of cases are associated metabolic disease and steatohepatitis. Inflammation associated with many liver disease, seems to be a necessary pre-requisite for successful tumor initiation. Mechanisms that link high fat diet and inflammation initial stage of HCC are not completely understood. The present work was designed to investigate the effect of fat, through modulation of the insulin-like growth factors I and II (IGF-I and IGF-II), on the promotion of hepatocellular carcinoma, and the role of cyclooxygenase 2 (COX-2). METHODS: two main groups of rats were used: control and HCC groups. The HCC group was further sub-divide in to two subgroups, HCC fed with standard diet and HCC fed with high fat diet. The effects of celecoxib were also investigated in HCC fed with high fat diet. RESULTS: We found that high fat diet was associated with significant increases in COX2 and interleukin 6 (IL6) with significant promotion of HCC progression. The significant increase in IGF could contribute partially to the observed effects of high fat diet. In addition, celecoxib was found to significantly reduce HCC progression. CONCLUSIONS: We conclude that COX2 could play central role in high prevalence of HCC observed with high fat diet. Several triggering factors such as IGF and IL6, together with the direct modulation of fat metabolism could open several novel preventive strategies of celecoxib treatment, and could be useful biomarkers for assessment of its pharmacological effects.

Complicated Whipple's disease and endocarditis following tumor necrosis factor inhibitors.

AIM: To test whether treatment with tumor necrosis factor inhibitors (TNFI) is associated with complications of Tropheryma whipplei (T. whipplei) infection. METHODS: Because unexplained arthritis is often the first Whipple's disease (WD) symptom, patients may undergo treatment with TNFI before diagnosis. This may influence the course of infection with T. whipplei, which causes WD, because host immune defects contribute to the pathogenesis of WD. A literature search and cross referencing identified 19 reports of TNFI treatment prior to WD diagnosis. This case-control study compared clinical data in patients receiving TNFI therapy (group I, n = 41) with patients not receiving TNFI therapy (group II, n = 61). Patients from large reviews served as controls (group III, n = 1059). RESULTS: The rate of endocarditis in patient group I was significantly higher than in patient group II (12.2% in group I vs 1.6% in group II, P < 0.05), and group III (12.2% in group I vs 0.16% in group III, P < 0.01). Other, severe systemic or local WD complications such as pericarditis, fever or specific organ manifestations were increased also in group I as compared to the other patient groups. However, diarrhea and weight loss were somewhat less frequent in patient group I. WD is typically diagnosed with duodenal biopsy and periodic acid Schiff (PAS) staining. PAS-stain as standard diagnostic test had a very high percentage of false negative results (diagnostic failure in 63.6% of cases) in group I. Polymerase chain reaction (PCR) for T. whipplei was more accurate than PAS-stainings (diagnostic accuracy, rate of true positive tests 90.9% for PCR vs 36.4% for PAS, P < 0.01). CONCLUSION: TNFI trigger severe WD complications, particularly endocarditis, and lead to false-negative PAS-tests. In case of TNFI treatment failure, infection with T. whipplei should be considered.

Assessing oral candidal carriage with mixed salivary glucose levels as non-invasive diagnostic tool in type-2 diabetics of davangere, karnataka, India.

BACKGROUND: The health of oral tissues is known to be related to salivary flow and its composition which may be altered in diabetic patients. The purpose of this study is to correlate mixed salivary glucose levels and oral candidal carriage and to assess the prevalence of candidal carriage in diabetics and controls. METHODS: Thirty adults with type-2 diabetes and 30 without diabetes (control subjects), aged 30-60 yr, participated in the study. Unstimulated saliva was collected and investigated for glucose levels (using glucose oxidase method) and colony-forming units (CFU) of Candida, this was stained with two stains, periodic acid-schiff stain and Grocott Gomori stain. RESULTS: In the present study mixed salivary glucose concentration in diabetics was significantly higher (p<0.01) compared to the controls. Diabetics with intraoral candidal carriage had higher salivary glucose levels (mean = 12.76±5.85 mg/dl) compared to cases where Candida was not isolated. The diabetics without intraoral candidal carriage had lower salivary glucose levels (mean = 5.36±2.24 mg/dl). This relationship could be seen in controls (non-diabetics) also. Diabetics showed an oral candidal carriage rate of 80% which was significantly higher compared to nondiabetics who showed an oral candidal carriage rate of 40%. CONCLUSION: Mixed salivary glucose levels were significantly higher in diabetics. The possible high salivary glucose level could predispose to oral candidal infection. So saliva can be used as a quick, non-invasive tool to assess the oral candidal status and possible infection.

The influence of angiotensin-(1-7) Mas receptor agonist (AVE 0991) on mitochondrial proteome in kidneys of apoE knockout mice.

Excessive action of angiotensin II on mitochondria has been shown to play an important role in mitochondrial dysfunction, a common feature of atherogenesis and kidney injury. Angiotensin-(1-7)/Mas receptor axis constitutes a countermeasure to the detrimental effects of angiotensin II on AT1 receptors. The aim of the study was to assess the effects of angiotensin-(1-7) peptidomimetic AVE0991 on the kidney mitochondrial proteome in widely used animal model of atherosclerosis (apoE(-/-) mice). Proteins changed in apoE(-/-) mice belonged to the groups of antioxidant enzymes, apoptosis regulators, inflammatory factors and metabolic enzymes. Importantly, AVE0991 partially reversed atherosclerosis-related changes in apoE(-/-) mice.

Rhinosporidiosis in the parotid duct: a rare case report.

Endemic to South India and Sri Lanka, Rhinosporidiosis is a chronic granulomatous infection caused by an agent of uncertain taxonomy: Rhinosporidium seeberi. Although it commonly manifests as a proliferative nasal lesion, many cases of Rhinosporidiosis have been reported where it has appeared as an extranasal lesion. The reported extranasal sites include the eye, ear, trachea, and parotid duct. However, the involvement of the parotid duct is quite rare, even among extranasal sites. The case presented is an adult female from the non-endemic zone of East India with a proliferative mass in the parotid duct. Although Rhinosporidiosis was not taken into consideration in the clinical differential diagnosis, eventual histopathological diagnosis confirmed Rhinosporidiosis. As this appears to be the second case of Rhinosporidiosis in the parotid duct in East India in 4 years, we encourage clinicians to be flexible in the differential diagnosis of proliferative growth in the parotid duct, even in those from non-endemic areas.

Acinar cell carcinoma: a rare pancreatic malignancy.

Acinar cell carcinoma of the pancreas is a rare pancreatic malignancy, constituting only 1-2% of all the pancreatic tumors. A young adult male presented with chronic diarrhea and upper abdominal pain, on investigations was found to have a large pancreatic tumor of size 12×7.5 cm involving the body of the pancreas. Pancreatic body and tail resection with splenectomy was done and final histopathological examination showed acinar cell carcinoma of the pancreas. Prognosis of acinar cell carcinoma is better than adenocarcinoma of the pancreas.

Oral discoid lupus erythematosus: A study of twenty-one cases.

AIMS: This study was undertaken to analyze the histopathological findings of oral discoid lupus erythematosus with conventional light microscopy for early diagnosis of the oral lesions that would aid in prompt treatment. OBJECTIVES: To find out the predominant age, sex, site and clinical features of oral discoid lupus erythematosus. To study the histopathological features of oral discoid lupus erythematosus. To study the alterations of basement membrane changes of oral discoid lupus erythematosus. MATERIALS AND METHODS: Our study consisted 21 cases of diagnosed DLE with oral lesions. A detailed clinical proforma was used for thorough clinical examination and light microscopy was used for histopathological study of the incisional biopsy specimens. STATISTICAL ANALYSIS USED: The lesions were diagnosed on the histopathological criteria given by Gisslen et al. and was statistically analyzed using the Chi square test. RESULTS: In the present study 9.52% patients had only oral lesions, while 90.47% patients had oral lesions along with skin lesions with the most common site of oral involvement being labial mucosa (76.19%), vermillion border (71.42%) and buccal mucosa (42.85%). On clinical examination, white spots were present in 28.6%, ulcers in 19% and central erythema in 52.4% lesions. Histopathologically, atrophy was observed in 66.66% cases, acanthosis in 66.66% and acanthosis alternating with atrophy in 33.33% cases along with the basement membrane appearing thin and homogenous in 66.7% and partially destroyed in 81% cases with Periodic Acid Schiff stain. CONCLUSIONS: Thus, from this study it was found that a diagnosis of oral discoid lupus erythematosus was based on the combination of clinical and histopathological findings. Thus the dentist may be in an important position to establish the diagnosis with the aid of clinical and histopathological findings before the cutaneous lesions become apparent.

Cutaneous metastasis from visceral malignancy: A rare presentation.

Cutaneous metastasis is an uncommon manifestation of visceral malignancy and a grave prognostic indicator. In extremely rare cases it may be the presenting sign of underlying malignancy. Here we report two cases of carcinoma gall bladder that presented with skin nodule. Fine needle aspiration cytology of these nodules revealed metastatic deposits of adenocarcinoma and was instrumental in establishing the primaries.