The critical impacts of cytokine storms in respiratory disorders.

Cytokine storm (CS) refers to the spontaneous dysregulated and hyper-activated inflammatory reaction occurring in various clinical conditions, ranging from microbial infection to end-stage organ failure. Recently the novel coronavirus involved in COVID-19 (Coronavirus disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been associated with the pathological phenomenon of CS in critically ill patients. Furthermore, critically ill patients suffering from CS are likely to have a grave prognosis and a higher case fatality rate. Pathologically CS is manifested as hyper-immune activation and is clinically manifested as multiple organ failure. An in-depth understanding of the etiology of CS will enable the discovery of not just disease risk factors of CS but also therapeutic approaches to modulate the immune response and improve outcomes in patients with respiratory diseases having CS in the pathogenic pathway. Owing to the grave consequences of CS in various diseases, this phenomenon has attracted the attention of researchers and clinicians throughout the globe. So in the present manuscript, we have attempted to discuss CS and its ramifications in COVID-19 and other respiratory diseases, as well as prospective treatment approaches and biomarkers of the cytokine storm. Furthermore, we have attempted to provide in-depth insight into CS from both a prophylactic and therapeutic point of view. In addition, we have included recent findings of CS in respiratory diseases reported from different parts of the world, which are based on expert opinion, clinical case-control research, experimental research, and a case-controlled cohort approach.

Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model.

Regeneration is a rare occurrence in the animal kingdom, but the earthworm stands out as a remarkable example of this phenomenon. Recent research has highlighted the promising wound healing properties of extracts derived from earthworms. Therefore, we propose that earthworm granulation tissue extract (EGTE) may facilitate wound healing by regulating immune responses in a rabbit diabetic wound model. Electron microscopy reveals that 70 % EGTE possesses noteworthy porosity with spherical to irregularly oval configuration. Gas chromatography-mass spectrometry (GC-MS) Characterization of EGTE revealed higher levels of ergosta-5,7,22-trien-3-ol, (3. beta.,22E). In-Vitro studies revealed significant anti-oxidant, anti-inflammatory and anti-bacterial properties in dose dependent manner. Likewise, cytotoxicity assessments reveal that 70 % EGTE exhibits minimal harm to cells while displaying substantial antioxidant and anti-inflammatory activities. For In-Vivo studies excision wounds were created on the dorsal regions of the experimental animals and were divided as Group I (50 % EGTE), Group II (70 % EGTE), Group III (vehicle) and Group IV (distilled water). Over a 21-day observation period 70 % EGTE facilitated the early healing of wounds in the experimental animals, evident through prompt wound closure, granulation tissue formation, increased DNA content, enhanced tensile strength of the wound area and enhanced the expression/synthesis of wound healing markers/proteins. From these results it can be postulated that EGTE accelerates wound healing by immune modulation, dampening of inflammatory pathway and enhanced expression of growth markers. Henceforth making it promising candidate for therapeutic use in diabetic wound healing.

Novel Therapeutic Agents for Management of Diabetes Mellitus: A Hope for Drug Designing against Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM.

Initial Experience Of Percutaneous Nephrolithotomy In Hazara Region.

BACKGROUND: Renal stone disease affects a large population of the world and surgical management is the main stay treatment for larger stones. In comparison to open procedures, percutaneous nephrolithotomy (PCNL) has been known to offer almost similar stone clearance with least patient morbidity. The study was done with the objectives to evaluate our initial experience of PCNL in the management of nephrolithiasis in Abbottabad. METHODS: A case series study was carried out at a private hospital, Valley Medical Complex, Abbottabad, including the 35 patients undergoing PCNL from January 2015 to February 2016. RESULTS: Thirty-five patients (23 male (65.7%) and 12 female (34.3%) underwent PCNL with a mean age of 35.57 years±6.701 and mean renal stones size of 24.49 mm±7.098. 28.6% stones (n=10) were located in the renal pelvis, 28.6% (n=10) in the lower pole of kidney and 42.9% (n=15) had stones in other sites of kidney. 25.7% patients (n=9) had mild, 57.1% (n=20) moderate and 17.1% (n=6) had gross hydronephrosis. 28.6% patients (n=10) had a single renal stone, 61.4% (n=18) had ≥2 stones whereas 7 patients (20%) had partial stag horn stone. Tract access was gained through upper pole in 8.6% patients (n=3), middle pole in 11.4% (n=2), and lower pole in 85.7% (n=30). Complete stone clearance was achieved in 30 patients (85.7%) whereas partial clearance accomplished in 3 patients (8.6%). Two patients had PCNL failure due to failed tract access. Postoperatively 10 patients (28.6%) had significant pain, 06 patients (17.1%) had fever and 1 patients (2.9%) required blood transfusion. CONCLUSIONS: PCNL is a safe procedure for management of upper urinary tract stones and is still in evolution stages in Hazara region.

Universal salt iodization is successful in Kashmiri population as iodine deficiency no longer exists in pregnant mothers and their neonates: Data from a tertiary care hospital in North India.

INTRODUCTION: Normal pregnancy results in a number of important physiological and hormonal changes that alter thyroid function. In pregnancy, the thyroid gland being subjected to physiological stress undergoes several adaptations to maintain sufficient output of thyroid hormones for both mother and fetus. Consequently, pregnant women have been found to be particularly vulnerable to iodine deficiency disorders (IDD), and compromised iodine status during pregnancy has been found to affect the thyroid function and cognition in the neonates. OBJECTIVES: Two decades after successful universal salt iodization (USI) in the country, there is scarce data on the iodine status of the pregnant women and their neonates. This is more relevant in areas like Kashmir valley part of sub-Himalayan belt, an endemic region for IDD in the past. The objective was to estimate Urinary Iodine status in pregnant women, the most vulnerable population. MATERIALS AND METHODS: We studied thyroid function [free T3 (FT3), T3, free T4 (FT4), T4, thyroid stimulating hormone (TSH)] and urinary iodine excretion (UIE) in the 1(st), 2(nd), and 3(rd) trimesters and at early neonatal period in neonates in 81 mother-infant pairs (hypothyroid women on replacement) and compared them with 51 control mother-infant pairs (euthyroid). RESULTS: Mean age of cases (29.42 + 3.56 years) was comparable to that of controls (29.87 + 3.37 years). The thyroid function evaluation done at baseline revealed the following: FT3 2.92 ± 0.76 versus 3.71 ± 0.54 pg/ml, T3 1.38 ± 0.37 versus 1.70 ± 0.35 ng/dl, FT4 1.22 ± 0.33 versus 1.52 ± 0.21 ng/dl, T4 9.54 ± 2.34 versus 13.55 ± 2.16 µg/dl, and TSH 7.92 ± 2.88 versus 4.14 ± 1.06 µIU/ml in cases versus controls (P > 0.01), respectively. The 2(nd) to 6(th) day thyroid function of neonates born to case and control mothers revealed T3 of 1.46 ± 0.44 versus 1.48 ± 0.36 ng/dl, T4 of 12.92 ± 2.57 versus 11.76 ± 1.78 µg/dl, and TSH of 3.64 ± 1.92 versus 3.82 ± 1.45 µIU/ml, respectively. DISCUSSION: UIE was similar (139.12 ± 20.75 vs. 143.78 ± 17.65 µg/l; P = 0.8), but TSH values were higher in cases (7.92 ± 2.88) as compared to controls (4.14 ± 1.06). Although UIE gradually declined from 1(st) trimester to term, it remained in the sufficient range in both cases and controls. Thyroid function and UIE was similar in both case and control neonates. CONCLUSION: We conclude that pregnant Kashmiri women and their neonates are iodine sufficient, indicating successful salt iodization in the community. Large community-based studies on thyroid function, autoimmunity, malignancies, etc., are needed to see the long-term impact of iodization.

Trans urethral electric vaporisation of prostate as an alternate to trans urethral resection in benign prostatic hyperplasia.

BACKGROUND: There is an impression that trans urethral electric vaporisation of prostate (TUEVP) is a relatively safe surgical procedure for obstructing benign prostates, however before considering it an alternative to Trans urethral resection (TURP) in our setting. we conducted this study to assess its safety. convenience and especially cost effectiveness in our practice. METHODS: Fifty patients with signs of benign prostatic enlargement causing acute urinary retention were selected and divided into two equal groups A and B. Patients of group A underwent TURP while the group B patients had TUEVP. Postoperative follow up to assess the results of the surgeries, including noting the complication rate, began 24 hour after the catheter was removed, continuing during postoperative visits of the patient at 2 weeks, 3 months and finally 6 months. RESULTS: For approximately same size prostate, the mean operation time was less for TUEVP as compared to the TURP. The mean volume of irrigating fluid used and the number of blood transfusions required was also less in the TUEVP patients. In addition. TURP patients were also noted to have slight postoperative hyponatraemia. Clot retention was more frequent in the TURP group than the TUEVP group. Urethral catheters were required for longer duration (mean duration 74.88 hrs vs 24hrs, p=0.0001) and so was the hospital stay (mean duration 6.25 days vs 4.4 days. p=0.0046) in the TURP group patients. Total mean cost of treatment was also higher in the patients undergoing TURP. Among the complications, only the peroperative blood transfusion rate was higher in the TURP patients as noted above. CONCLUSIONS: The TURP has slightly higher morbidity and is costlier than TUEVP but its results in terms of relieving outflow obstruction are significantly better than TUEVP. It is therefore concluded that TURP is a more effective procedure but TUEVP with lesser morbidity and cost, is more suitable for relatively lesser obstructions in our setting.