Medullary carcinoma of thyroid metastasis to breast: A cytological experience

Medullary carcinoma of thyroid is a relatively uncommon malignancy, which can be sporadic and syndromic in nature. It commonly spreads to regional lymph nodes followed by spreading to distant sites. Breast is an uncommon site of metastasis of this malignancy. Our case is a 38‐year‐old woman married parous woman presenting to the outpatient department with complaints of lump in both the breasts. Fine‐needle aspiration (FNA) was attempted, which revealed a malignancy more suggestive of a metastasis, which was confirmed on CT scan. A detailed history revealed that the patient is a known case of medullary carcinoma of thyroid. The report was given as metastatic medullary carcinoma to the breast after confirming with a calcitonin immunostain. Given the versatility of primary lesions in the breast, minimally invasive FNA cytology (FNAC) technique with adequate sampling helps in identifying metastatic lesions. Differentiating primary from metastatic lesions changes the course of management to the patient. Metastatic lesions should always be kept in mind in the occurrence of known malignancies, however rare the site of occurrence may be. Morphological clues and immunohistochemical work up aid in arriving at correct diagnosis.     

Surgical management of hepatic arterioportal fistula in a neonate

Congenital arterioportal fistulae in the liver are rare malformations which can lead to portal hypertension. We report a hepatic arterioportal fistula in a neonate who presented with intestinal hypoperfusion. Computerised tomography angiography showed a fistulous communication between the left hepatic artery and portal vein with hypoperfusion of small and large bowel. A formal left hepatectomy was done followed by clinical improvement and reduction in portal venous pressures. The case and the literature pertaining to it are discussed.     

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography–tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11–13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m² with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m² (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.     

Assessment of retinal manifestations of Parkinson’s disease using spectral domain optical coherence tomography: A study in Indian eyes

Purpose:To assess the retinal manifestations of Parkinson’s disease using optical coherence tomography.Methods:A prospective case-control study comparing 30 eyes from 15 patients with Parkinson’s disease and 22 eyes from 11 healthy age-matched controls. Total macular subfield thickness and the thickness of the ganglion cell layer, nerve fiber layer, and peripapillary retinal nerve fiber layer were measured with spectral-domain optical coherence tomography (SD-OCT).Results:The mean age of PD patients was 68.4 years ± 10.64 (range: 46–82) and in the control group was 66.36 ± 5.22 (range: 64–68). The average disease duration in patients with PD was 6.7 ± 2.8 years (range: 2–10 years). The mean best-corrected visual acuity in PD was 20/26 and 20/20 in controls, with P = 0.0059, which was significant. Significant difference was also found in the contrast sensitivity between both groups. Structural differences in the central macular thickness (P = 0.0001), subfield thicknesses in the superior (P = 0.003), inferior (P = 0.001), nasal (P = 0.004), and temporal subfields (P = 0.017) was seen. Severe thinning of the ganglion cell layer was seen in PD patients (P = 0.000) as well as of the nerve fiber layer (P = 0.004). Peripapillary retinal nerve fiber thickness measured showed significant thinning in superotemporal (P = 0.000), superonasal (P = 0.04), inferonasal (P = 0.000), inferotemporal (P = 0.000), nasal (P = 0.000), and temporal quadrants (P = 0.000).Conclusion:Visual dysfunction was observed in patients with PD along with structural alterations on OCT, which included macular volumes, ganglion cell layer, and peripapillary retinal nerve fiber layer.     

A benzothiazole-based new fluorogenic chemosensor for the detection of CN− and its real-time application in environmental water samples and living cells

Since the cyanide ion is used in a wide range of industries and is harmful to both human health and the environment, a number of research efforts are dedicated to creating fluorescence sensors for the detection of cyanide (CN⁻). Herein, for the fluorescence detection of CN⁻, a new highly selective and sensitive sensor 2-(3-(benzo[d]thiazol-2-yl)-4-hydroxybenzylidene)-1H-indene-1,3(2H)-dione (BID) was created by conjugating a benzothiazole moiety with 1H-indene-1,3(2H)-dione. The donor and acceptor components of this hybrid receptor were covalently connected through a double bond. The nucleophilic addition of a cyanide anion to the BID inhibits the intramolecular charge transfer (ICT) transition, resulting in spectral and colour alterations in the receptor. When the solvent polarity was increased from n-hexane to methanol, this molecule exhibited a bathochromic shift in the emission wavelength (610 to 632 nm), suggesting the presence of a solvatochromic action. The sensor BID has shown strong specificity towards CN⁻ by interrupting its internal charge transfer (ICT), resulting in a significant change in the UV-vis spectrum and a notable blue shift in the fluorescence emission spectrum. The cyanide anion (CN⁻) is responsible for the optical alterations observed by BID, as opposed to the other anions examined. The detection limit was 5.97 nM, significantly less than the WHO''s permitted amount of CN⁻ in drinking water. The experimental findings indicate that BID''s fluorescence response to CN⁻ is pH insensitive throughout a wide pH range of 6.0 to 12.0. The interaction mechanism between the BID and CN⁻ ions has been studied by HRMS, ¹H-NMR titration experiments, FT-IR, and DFT, which confirmed the nucleophilic addition of CN⁻ on vinylidene and subsequent disturbance of ICT. Additionally, we demonstrated the real-time detection application of CN⁻ in environmental water samples and live-cell imaging.

Since the cyanide ion is used in a wide range of industries and is harmful to both human health and the environment, a number of research efforts are dedicated to creating fluorescence sensors for the detection of cyanide (CN⁻).     

Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability

1. Download : Download high-res image (382KB)
2. Download : Download full-size image

     

Structural and functional analysis of de‐N‐acetylase PgaB from periodontopathogen Aggregatibacter actinomycetemcomitans

The oral pathogen Aggregatibacter actinomycetemcomitans uses pga gene locus for the production of an exopolysaccharide made up of a linear homopolymer of β‐1,6‐N‐acetyl‐d ‐glucosamine (PGA). An enzyme encoded by the pgaB of the pga operon in A. actinomycetemcomitans is a de‐N‐acetylase, which is used to alter the PGA. The full length enzyme (AaPgaB) and the N‐terminal catalytic domain (residues 25–290, AaPgaBN) from A. actinomycetemcomitans were cloned, expressed and purified. The enzymatic activities of the AaPgaB enzymes were determined using 7‐acetoxycoumarin‐3‐carboxylic acid as the substrate. The AaPgaB enzymes displayed significantly lower de‐N‐acetylase activity compared with the activity of the deacetylase PdaA from Bacillus subtilis, a member of the CE4 family of enzymes. To delineate the differences in the activity and the active site architecture, the structure of AaPgaBN was determined. The AaPgaBN structure has two metal ions in the active site instead of one found in other CE4 enzymes. Based on the crystal structure comparisons among the various CE4 enzymes, two residues, Q51 and R271, were identified in AaPgaB, which could potentially affect the enzyme activity. Of the two mutants generated, Q51E and R271K, the variant Q51E showed enhanced activity compared with AaPgaB, validating the requirement that an activating aspartate residue in the active site is essential for higher activity. In summary, our study provides the first structural evidence for a di‐nuclear metal site at the active site of a member of the CE4 family of enzymes, evidence that AaPgaBN is catalytically active and that mutant Q51E exhibits higher de‐N‐acetylase activity.     

Animal models for SARS-CoV-2 and SARS-CoV-1 pathogenesis,transmission and therapeutic evaluation

There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections. The coronavirus family, which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2, crossed the species barrier and infected humans, causing a global outbreak in the 21^st century. Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials, animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines. The ideal animal models should reflect the viral replication, clinical signs, and pathological responses observed in humans. Different animal species should be tested to establish an appropriate animal model to study the disease pathology, transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019. In this context, the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.     

Perforation of Jejunal Diverticula in Steroids and Nonsteroidal Anti-Inflammatory Drug Abusers: A Case Series

INTRODUCTION: Jejunal diverticula are rare lesions, and when complications arise, they pose diagnostic difficulties. Perforation is a common complication resulting in an acute abdomen, although preoperative diagnosis is usually not possible. The "gold standard" for management for patients with complications is surgery. We present a series of patients with perforated jejunal diverticula who were on prolonged treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for Chikungunya fever. METHODS: There were a total of six patients, all of them presenting with perforative peritonitis, with or without shock. Plain abdominal radiogram and ultrasonogram confirmed this, although the exact site of the perforation was not diagnosed preoperatively. All patients underwent exploratory laparotomy and perforated jejunal diverticulum was found. Resection and anastomosis was performed in all cases. RESULTS: The mean operating time was 113.5 minutes, and the blood loss was not significant. Postoperative course was uneventful except wound infection in two patients. There was no mortality. CONCLUSIONS: Prolonged NSAID and steroid use are known to cause ulceration/perforation of the upper digestive tract and colonic diverticula. This seems to be the most likely cause for the perforation of jejunal diverticula in our series of patients. This view is supported by the absence of inflammation and infiltration of neutrophils on histopathological examination of the diverticula.     

Management of upper limb arterial injury without angiography--Chennai experience

We present our experience and observations in the management of upper limb arterial injury in a tertiary trauma care centre of a University Hospital in a developing country from January 2000 to January 2002. In this retrospective study, we had treated 27 patients (identified from trauma register) with upper extremity vascular injuries. Clinical examination and Doppler pressure studies were our prime modalities of investigation. Angiography was not employed. Our immediate limb salvage rate was 100%. Two patients developed complications during a mean follow up of 70 days with one requiring amputation. We thereby emphasise the fact that good results can be obtained by thorough clinical examination and Doppler evaluation and prompt surgery without the need for angiography in upper limb vascular trauma.