Allyl piperidine-1-carbodiothioate and benzyl 1H-imidazole 1 carbodithioate: two potential agents to combat against mycobacteria.

AIMS: The emergence of multidrug resistant strains of Mycobacterium tuberculosis has made tuberculosis more difficult to manage clinically. With the aim of obtaining new and effective anti-mycobacterial agent(s), this study investigated the anti-mycobacterial activity of several imidazole and piperidine derivatives. METHODS AND RESULTS: Towards obtaining new anti-mycobacterial agents, Mycobacterium smegmatis cells were treated with different compounds for their growth inhibitory activity. Among these, benzyl 1H-imidazole-1-carbodithioate and allyl piperidine-1-carbodiothioate exhibited better inhibition than the others. Thereafter, anti-biofilm property of these two was examined by treating M. smegmatis with these agents before and after the formation of biofilm. The result showed that both the compounds at their sublethal dose inhibited the formation of biofilm as well as dispersed preformed biofilm. Consistently, they augmented the activity of isoniazid or rifampicin against biofilm-encapsulated cells. MTT assay was performed to examine the toxic effects of this combinatorial therapy on different cell lines. Results exhibited a low cytotoxicity for this combinatorial treatment. The activity of these two was also verified against dormant mycobacterial cells and was found to be effective. CONCLUSION: The present study identified two compounds that exhibited anti-mycobacterial activities against both planktonic and dormant cells. These two also exhibited anti-biofilm activity at their sublethal dose and augmented the activity of isoniazid and rifampicin against biofilm encapsulated cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The current study provides two new agents that have the potential to be used in anti-mycobacterial therapy and may help in public health management.

Hyperthyroxinemia with a non-suppressed TSH: how to confidently reach a diagnosis in this clinical conundrum.

Disorders of thyroid function are among the commonest referrals to endocrinology. While interpretation of thyroid function testing is usually straightforward, accurate interpretation becomes significantly more challenging when the parameters do not behave as would be expected in normal negative feedback. In such cases, uncertainty regarding further investigation and management arises. An important abnormal pattern encountered in clinical practice is that of high normal or raised free thyroxine (fT4) with inappropriately non-suppressed or elevated thyroid-stimulating hormone (TSH). In this short review using two clinical vignettes, we examine the diagnostic approach in such cases. A diagnostic algorithm is proposed to ensure that a definitive diagnosis is reached in these challenging cases.

Cytohistological correlation in pituitary tumor and immunological assessment with the help of Ki-67.

BACKGROUND: Tumors of the pituitary gland and sellar region represent approximately 10-15% of all brain tumors. Pituitary adenoma (PA), the most common pathology of the pituitary gland, can be effectively subclassified only with the help of immunohistochemistry (IHC). This is important and needed for individual patient management. AIMS AND OBJECTIVES: The objective of the study was to analyze the importance of intraoperative imprint smear cytology and correlating with final histopathological diagnosis. Furthermore, to classify the different types of PA with the help of IHC, prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH) and to predict the benign, atypical, or malignant nature of the tumor with the help of prognostic marker Ki-67. MATERIALS AND METHODS: A prospective study was done in 34 cases. The patients whose pituitary gland samples are referred from the endocrine and the neurosurgery department to the pathology department for histopathological examinations were selected. We have studied the clinical features, radiology and touch imprint cytology, histopathology, and IHC with the help of PRL, ACTH, GH, and Ki-67 of PA over 2 years. RESULTS: In our study, we had 32 cases of PA of 34 cases over a span of 2 years. We have seen that there is a correlation between cytological and histological diagnosis of the subtypes of PA in 62% cases, and the Kappa statistics show a moderate extent of agreement (Kappa - 0.320, 95% confidence interval = 0.031-0.609). Ki-67 when compared to the radiological grading showed a high degree of comparability (Chi-square test: P < 0.001). All cases with invasion had a higher Ki-67. On using the Fisher's exact test, we found that the Ki-67 expression with GH-producing adenomas and ACTH-producing adenomas was comparable (P = 1.000) while in PRL-producing adenomas too this was not significant (P = 0.269). CONCLUSION: PA can be effectively classified with the help of IHC. Intraoperative cytology is important in diagnosing PA, but histopathology remains the gold standard in diagnosing and differentiating PA from other pathologies of the pituitary gland. The radiological grading together with immunological classification and the prognostic markers of Ki-67 is important in deciding the benign or atypical nature of the adenomas thus helping in better patient management.

Free radicals and antioxidant status in protein energy malnutrition.

Background/Objectives. The aim of this study was to evaluate oxidant and antioxidant status in children with different grades of Protein Energy Malnutrition (PEM). Subjects/Methods. A total of two hundred fifty (250) children (age range: 6 months to 5 years) living in eastern UP, India, were recruited. One hundred and ninety-three (193) of these children had different grades of PEM (sixty-five (65) children belong to mild, sixty (60) to moderate, and sixty-eight (68) to severe group). Grading in group was done after standardization in weight and height measurements. Fifty-seven (57) children who are age and and sex matched, healthy, and well-nourished were recruited from the local community and used as controls after checking their protein status (clinical nutritional status) with height and weight standardization. Redox homeostasis was assessed using spectrophotometric/colorimetric methods. Results. In our study, erythrocyte glutathione (GSH), plasma Cu, Zn-superoxide dismutase (Cu,Zn-SOD,EC 1.15.1.1), ceruloplasmin (Cp), and ascorbic acid were significantly (P < 0.001) more decreased in children with malnutrition than controls. Plasma malondialdehyde (MDA), and protein carbonyl (PC) were significantly (P < 0.001) raised in cases as compared to controls. Conclusion. Stress is created as a result of PEM which is responsible for the overproduction of reactive oxygen species (ROSs). These ROSs will lead to membrane oxidation and thus an increase in lipid peroxidation byproducts such as MDA and protein oxidation byproducts such as PC mainly. Decrease in level of antioxidants suggests an increased defense against oxidant damage. Changes in oxidant and antioxidant levels may be responsible for grading in PEM.

Serum catalytic Iron: A novel biomarker for coronary artery disease in patients on maintenance hemodialysis.

Cardiovascular disease is the leading cause of morbidity and mortality in maintenance hemodialysis (MHD) patients. We evaluated the role of serum catalytic iron (SCI) as a biomarker for coronary artery disease (CAD) in patients on MHD. SCI was measured in 59 stable MHD patients. All patients underwent coronary angiography. Significant CAD was defined as a > 70% narrowing in at least one epicardial coronary artery. Levels of SCI were compared with a group of healthy controls. Significant CAD was detected in 22 (37.3%) patients, with one vessel disease in 14 (63.63%) and multi-vessel disease in eight (36.36%) patients. The MHD patients had elevated levels of SCI (4.70 ± 1.79 µmol/L) compared with normal health survey participants (0.11 ± 0.01 µmol/L) (P < 0.0001). MHD patients who had no CAD had SCI levels of 1.36 ± 0.34 µmol/L compared with those having significant CAD (8.92 ± 4.12 µmol/L) (P < 0.0001). Patients on MHD and diabetes had stronger correlation between SCI and prevalence of CAD compared with non-diabetics. Patients having one vessel disease had SCI of 8.85 ± 4.67 µmol/L versus multi-vessel disease with SCI of 9.05 ± 8.34 µmol/L, P = 0.48. In multivariate analysis, SCI and diabetes mellitus were independently associated with significant CAD. We confirm the high prevalence of significant CAD in MHD patients. Elevated SCI levels are associated with presence of significant coronary disease in such patients. The association of SCI is higher in diabetic versus the non-diabetic subgroup. This is an important potentially modifiable biomarker of CAD in MHD patients.

Congenital duodenal obstruction with preduodenal portal vein and situs inversus totalis: report of two cases and literature review.

Preduodenal portal vein is a rare congenital anomaly that causes high intestinal obstruction. The authors report two interesting cases of preduodenal portal vein that were diagnosed as having congenital duodenal obstruction. As there is a high potential for surgical risk, this anomaly is of special interest to the surgeon and should be kept in mind. Here, we discuss the clinical presentation, diagnosis and management along with a review of the literature.

Effects of deterministic and random refuge in a prey-predator model with parasite infection.

Most natural ecosystem populations suffer from various infectious diseases and the resulting host-pathogen dynamics is dependent on host's characteristics. On the other hand, empirical evidences show that for most host pathogen systems, a part of the host population always forms a refuge. To study the role of refuge on the host-pathogen interaction, we study a predator-prey-pathogen model where the susceptible and the infected prey can undergo refugia of constant size to evade predator attack. The stability aspects of the model system is investigated from a local and global perspective. The study reveals that the refuge sizes for the susceptible and the infected prey are the key parameters that control possible predator extinction as well as species co-existence. Next we perform a global study of the model system using Lyapunov functions and show the existence of a global attractor. Finally we perform a stochastic extension of the basic model to study the phenomenon of random refuge arising from various intrinsic, habitat-related and environmental factors. The stochastic model is analyzed for exponential mean square stability. Numerical study of the stochastic model shows that increasing the refuge rates has a stabilizing effect on the stochastic dynamics.

Potential application of the nisin Z preparation of Lactococcus lactis W8 in preservation of milk.

AIMS: The aim of the study is to evaluate the effectiveness of the preparation of nisin Z from Lactococcus lactis W8-fermented milk in controlling the growth of spoilage bacteria in pasteurized milk. METHODS AND RESULTS: Spoilage bacteria isolated from pasteurized milk at 8 and 15°C were identified as Enterococcus italicus, Enterococcus mundtii, Enterococcus faecalis, Bacillus thuringiensis, Bacillus cereus, Lactobacillus paracasei, Acinetobacter sp., Pseudomonas fluorescens and Enterobacter aerogenes. These bacteria were found to have the ability to survive pasteurization temperature. Except Enterobacter aerogenes, the spoilage bacteria were sensitive to the nisin Z preparation of the L. lactis W8. Addition of the nisin Z preparation to either the skim milk or fat milk inoculated with each of the spoilage bacteria reduced the initial counts (about 5 log CFU ml⁻¹) to an undetectable level within 8-20 h. The nisin Z preparation extended the shelf life of milk to 2 months under refrigeration. CONCLUSIONS: The nisin Z preparation from L. lactis W8-fermented milk was found to be effective as a backup preservative to counteract postpasteurization contamination in milk. SIGNIFICANCE AND IMPACT OF THE STUDY: A rapid inhibition of spoilage bacteria in pasteurized skim and fat milk with the nisin Z preparation of L. lactis W8 is more significant in comparison with the commercially available nisin (nisin A). The nisin Z preparation can be used instead of commercial nisin, which is not effective in fat milk.

Simultaneous presentation of type 1 diabetes and Graves' disease.

The association between type 1 diabetes mellitus and autoimmune thyroid disease is well documented in the literature. Both can coexist although one endocrinopathy usually precedes the other. The simultaneous new onset of both diseases is rarely seen. Hyperthyroidism can precipitate and complicate the management of diabetic ketoacidosis by masking its classical clinical features. Persistent tachycardia after correction of acidosis and dehydration, may be the only suggestion of another coexisting illness such as thyrotoxicosis. We describe the case of a previously healthy woman who developed new onset type 1 diabetes mellitus and Graves' disease, and presented with diabetic ketoacidosis.

Postoperative intussusception following repair of eventration of diaphragm--two case reports.

Two patients of postoperative intestinal obstruction following repair of eventration of diaphragm, subsequently diagnosed as postoperative intussusception managed successfully, are reported. Absence of common features of intussusception led to delay in the diagnosis. Rarity of this phenomenon and incidentally two consecutive cases of postoperative intussusception occurring after repair of eventration of diaphragm prompted to report these two cases.

Pyloric and antral strictures following corrosive acid ingestion: A report of four cases.

This study reports four children who developed complete stricture of pylorus and antrum of the stomach following accidental ingestion of corrosive agent (toilet cleaner).

Outcome of colostomy closure with different skin closure techniques in a developing country.

BACKGROUND: Colostomy site, which is a potentially contaminated wound, is traditionally closed with interrupted skin stitches and placement of intraperitoneal or parietal or both drains; often with poor cosmetic outcome in our country. This study aims at prospective evaluation of colostomy closure wounds by different techniques. PATIENTS AND METHODS: This study was carried out in all infants and children with colostomy (for different pathologies) admitted for colostomy closure in our institute from August 1, 2006 to February 29, 2008. Patients were divided into two groups: Group A with colostomy closure without any drain and subcuticular skin closure and Group B with colostomy closure with both intraperitoneal and parietal drain and interrupted skin closure. Patient's details, including age, sex, body weight, diagnosis, preoperative bowel preparation, peroperative antibiotics, postoperative wound infection, anastomotic leaks, duration of hospitalisation and postoperative follow-up for wound assessment, were recorded. By the end of February 2008, 151 cases of colostomy closure were recorded, 70 in Group A and 81 in Group B. RESULTS: Statistical analysis of the data showed no statistically significant difference in wound infection and anastomotic leak between the two groups. On postoperative follow-up, wound assessment showed significantly better cosmesis in the no drain subcuticular group. CONCLUSION: This study shows that closing colostomies without any drain and subcuticular skin closure does not result in any increased incidence of wound infection and has better cosmetic results.

Emergency separation of a xipho-omphalopagus twin in a developing country.

Female conjoined twins (thoraco-omphalopagus) were delivered by emergency caesarean section in a private nursing home. On examination, one of the twins was dead and was threatening the survival of the surviving twin (twin A). An emergency separation was performed to salvage the surviving twin.

Gastric teratoma in a female infant.

Gastric teratoma is a rare lesion seen most often in male infants. This patient, aged one year, female was having a massive benign gastric teratoma. The size of the tumour was 22 cm x 10 cm x 8 cm and weighted 2.250 kg making it one of the largest gastric teratoma. The tumour was removed by surgery. Histopathology revealed presence of all 3 elements in the form of skin, cartilage, fibrofatty tissue, blood vessels and gland with tall columnar epithelium. Postoperative period was uneventful.

Giant congenital infected splenic cyst: An interesting case report and review of the literature.

Splenic cysts are rare lesions. The congenital non-parasitic cysts of the spleen are rarely met in the clinical practice. Primary cysts have a cellular lining that can be caused by congenital events or parasitic infection (Echinococcus). Secondary cysts have no cellular lining and may be of hemorrhagic, serous, inflammatory, or degenerative origin. We report a rare case of congenital cyst of spleen in a child aged 10 years treated successfully by splenectomy because of total involvement of the splenic parenchyma along with involvement of hilum by the cyst, and we review the literature.

Role of gestation delay in a plankton-fish model under stochastic fluctuations.

The present paper studies a minimal prey-predator model in the context of marine plankton interaction together with predation by planktivorous fish. The time lag required for gestation of the predator is incorporated and the resulting delayed model is analyzed for stability and bifurcation phenomena. A stochastic extension of the model is considered by perturbing the growth process of phytoplankton using colored noise process known to be more appropriate for the marine environment. The stochastic models with and without gestation delay are analyzed for stability aspects and a threshold value of gestation delay is obtained; this threshold is then compared with that of the deterministic model.

Molecular modeling of the ternary complex of Rusticyanin-cytochrome c4-cytochrome oxidase: an insight to possible H-bond mediated recognition and electron transfer reaction in T. ferrooxidans.

The metabolism of Thiobacillus ferrooxidans involves electron transfer from the Fe+2 ions in the extracellular environment to the terminal oxygen in the bacterial cytoplasm through a series of periplasmic proteins like Rusticyanin (RCy), Cytochrome (Cyt c4), and Cytochrome oxidase (CcO). The energy minimization and MD studies reveal the stabilization of the three redox proteins in their ternary complex through the direct and water mediated H-bonds and electrostatic interaction. The surface exposed polar residues of the three proteins, i.e., RCy (His 143, Thr 146, Lys 81, Glu 20), Cyt c4 (Asp 5, 15, 52, Ser 14, Glu 61), and CcO (Asp 135, Glu 126, 140, 142, Thr 177) formed the intermolecular hydrogen bonds and stabilized the ternary complex. The oxygen (Oepsilon1) of Glu 126, 140, and 142 on subunit II of the CcO interact to the exposed side-chain and Ob atoms of the Asp 52 of Cyt c4 and Glu 20 and Leu 12 of RCy. The Asp 135 of subunit II also forms H-bond with the Nepsilon atom of Lys 81 of RCy. The Oepsilon1 of Glu 61 of Cyt c4 is also H-bonded to Ogamma atom of Thr 177 of CcO. Solvation followed by MD studies of the ternary protein complex revealed the presence of seven water molecules in the interfacial region of the interacting proteins. Three of the seven water molecules (W 79, W 437, and W 606) bridged the three proteins by forming the hydrogen bonded network (with the distances approximately 2.10-2.95 A) between the Lys 81 (RCy), Glu 61 (Cyt c4), and Asp 135 (CcO). Another water molecule W 603 was H-bonded to Tyr 122 (CcO) and interconnected the Lys 81 (RCy) and Asp 135 (CcO) through the water molecules W 606 and W 437. The other two water molecules (W 21 and W 455) bridged the RCy to Cyt c4 through H-bonds, whereas the remaining W 76 interconnected the His 53 (Cytc4) to Glu 126 (CcO) with distances approximately 2.95-3.0 A.

Acquired tracheo-oesophageal fistula: a case report.

This is a case report of a girl aged 4 years who presented with repeated attacks of chocking and dysphagia. She was diagnosed to be having an acquired tracheo- oesophageal fistula caused by fish bone impaction. She was treated successfully. In this report, the literature was reviewed of this rare condition.