Modulation of diabetes with gonadotropin-releasing hormone antagonists in the nonobese mouse model of autoimmune diabetes

The nonobese mouse model of autoimmune diabetes (NOD mouse) exhibits a strain-dependent preponderance of disease in females. Castration of male NOD mice leads to an increased incidence of diabetes, suggesting that testosterone directly modulates the expression of diabetes in the NOD mouse. However, castration also modulates hypothalamic and pituitary hormone production via removal of the negative feedback effects of testosterone. One hypothalamic hormone with immunomodulatory properties whose expression is increased by castration is GnRH. To test whether the increased incidence of diabetes in castrated male NOD mice is related to an increase in GnRH activity, we treated castrated male NOD mice with Antide, a GnRH receptor antagonist, to determine the effect on the incidence and timing of onset of diabetes. The prevalence of diabetes at 40 wk of age in male NOD mice was 50% in sham-operated mice, compared with an 83% prevalence in castrated males. Antide administration prevented the increased incidence of diabetes in the castrated male mice. Antide reduced total serum IgG levels, IL-6 cytokine expression in cultured splenocytes, and the lymphocytic infiltration of islets. GnRH administration exerted reciprocal effects, leading to earlier timing of onset of diabetes and increases in serum total IgG levels. We conclude that GnRH modulates the expression of diabetes in the NOD mouse independently of gonadal steroids.     

NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes — Possible implications for NOD2-associated Crohn''s disease

Sensing of commensal microorganisms via Toll-like receptors (TLR) in the gut is essential for maintaining intestinal homeostasis in healthy individuals. Conversely, Crohn's disease is characterised by an inappropriate T helper-type 1 (Th1)-mediated immune response towards these same microorganisms. NOD2 is expressed by dendritic cells (DC) and mediates responses to bacterial muramyl-dipeptides (MDP). Mutations in NOD2 (CARD15) have recently been associated with susceptibility to Crohn's disease although the underlying mechanisms have yet to be established. We investigated the functional outcome of NOD2 and TLR4-mediated activation in monocyte-derived DC from wild-type NOD2 healthy controls and NOD2 frame-shift mutation-carrying Crohn's disease patients. In wild-type DC, MDP acted synergistically with LPS to amplify inflammatory cytokine production, enhance co-stimulatory molecule expression, and produce DC that promoted the proliferation of naïve, allogeneic, CD4⁺ T lymphocytes with a Th2-like cytokine profile. By contrast, DC carrying homozygous NOD2 mutations were unable to react to MDP, responded to LPS only, and promoted the development of Th1 cells. These results suggest activation of the NOD2 pathway in DC modulates their response to TLR agonists and regulates their ability to induce polarised Th1 responses. As a consequence, Crohn's disease patients with defective NOD2 may be predisposed to the generation of strongly polarised Th1 responses against common commensal microorganisms.     

DISPOSABLE COVID BOX – A new invention

ObjectiveTo introduce a new method to do safe bronchoscopy, a highly aerosol generating procedure through disposable COVID box in this difficult COVID time.MethodsWe have introduced an unbelievably cheap and effective method “DISPOSABLE COVID BOX”. We took an acrylic board 70 × 20 cm and attached 3 bars 32 cm long and slide it under the side of the patient. A similar contraption is used on the other side. Then, it is covered by a polypropylene sheet 2’ × 2’. It makes a completely disposable airtight chamber with the polypropylene sheet. We make a 1 cm nick in the sheet and introduce the video-bronchoscope, which is further navigated into the patient without any discomfort either to the patient or Bronchoscopist. When the procedure is finished, scope is withdrawn from the patient and the polypropylene sheet is squeezed out. The polypropylene sheet is removed and disposed off with all precautions, and the acrylic boards and the bars are cleaned with 1% Sodium hypochlorite solution. This way, the cost is only of polypropylene sheet which is negligible.ResultsVideobronchoscopies in indicated patients were done using this novel disposable covid box. This new invention called Disposable COVID box has been practiced for the first time, it's an innovative technique about which we want the world to be known.ConclusionTo conclude, there are no aerosols released in atmosphere after the procedure, making it absolutely safe for bronchoscopist and at same time patient also remains safe. We are ready again in no time with fresh polypropylene sheet to do the next bronchoscopy.     

Opaque hemithorax - An interesting case

ObjectiveTo present an interesting case of left opaque hemithorax in an adult female and discuss its assessment and management.MethodsDesign: Case Report. Setting: Tertiary care hospital. Patient: One.Results44yrs retropositive female admitted with complaints of acute onset dry cough since 15–20 days, sudden breathlesness since 5 days which was progressive in nature, left sided heaviness in chest since 5 days. CECT Thorax showed complete collapse of left lung with cut off of left main bronchus while video bronchoscopy showed left main bronchus completely blocked with very thick necrotic mass and was difficult to dislodge. Debulking with cryo probe was done and left main bronchus was completely cleared off. Allergen panel showed very high serum IgE, high S.IgE against aspergillus and high specific S.IgG against aspergillus. Patient and her Chest X-ray showed significant improvement post cryo debulking and was discharged satisfactorily on oral voriconazole therapy.ConclusionEndobronchial aspergillosis is characterized by massive intrabronchial overgrowth of the aspergillus species, mainly aspergillus fumigatus. Most patients with chronic pulmonary aspergillosis, including those with simple aspergillomas and Aspergillus nodules, have positive Aspergillus IgG antibodies in the blood. We hereby present a case of 44 yrs female presenting with complaints of dry cough and dyspnea and was diagnosed with endobronchial aspergillosis with complete obliteration of left main bronchus by fungal debris in which cryo debulking was done which relieved the symptoms significantly and was discharged in satisfactory condition on oral voriconazole therapy.     

Protective effect of proteins derived from Calotropis procera latex against acute inflammation in rat

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Does Famotidine Reduce the Risk of Progression to Severe Disease,Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis

Background

Famotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19.

Aims

This study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

Methods

This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted.

Results

Five studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI?=?0.52–1.30, P?=?0.40).

Conclusion

Famotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

     

Differential diagnosis portfolio of a pediatric rheumatologist: eight cases,eight stories

Clinical Rheumatology - There is no single diagnostic test for any rheumatic disease. The diagnosis of a rheumatic disease is made by the sum of the findings in history, physical examination,...     

Increased systemic and regional coagulation activity in patients with mitral stenosis and sinus rhythm

A hypercoagulable state has been reported in patients with mitral stenosis (MS) and sinus rhythm (SR). However it has been suggested that the coagulation activity may be increased only within the left atrium in MS, with normal peripheral blood levels. The aim of the present study was to assess regional left atrial and systemic coagulation activities by measuring PF1+2 in patients with severe mitral stenosis and sinus rhythm, normal blood clotting times, and no left atrial thrombus. The study was conducted in 25 consecutive patients with moderate-to-severe MS and sinus rhythm who underwent percutaneous balloon mitral valvuloplasty. Transesophageal echocardiography was performed before the valvuloplasty procedure in all patients to exclude the presence of left atrial thrombus and left atrial spontaneous echo contrast (LASEC). There were no statistically significant differences between LASEC-positive and LASEC-negative patients with respect to age, gender, fibrinogen levels, prothrombin time, mitral valve area, mean mitral gradient, pulmonary artery pressure (in all p > 0.05). Regional (left atrial) PF1+2 levels of both LASEC-positive and LASEC-negative patients were significantly elevated when compared to control subjects (p < 0.01). Statistically significant elevated systemic level of PF1+2 was observed only in LASEC-positive patients when compared to control subjects (p < 0.01, p > 0.05, respectively). In conclusion patients with severe mitral stenosis and SR have increased regional coagulation activity in both LASEC-negative and LASEC-positive groups. Although this increased regional coagulation activity has been reflected in peripheral blood of LASEC-positive patients, it has not been reflected in peripheral blood of LASEC-negative patients.