Intriguing two-dimensional assembly of cobaloxime with a [Zn2(OOCR)4] center.

We report the synthesis and crystallographic studies of paddlewheel-based methyl cobaloxime assembly formed from methyl cobaloxime, isonicotinic acid, and Zn(NO(3))(2). The cobaloxime units are assembled over two-dimensional metal-organic polyhedra constructed from isonicotinate and Zn metal ions.

Chemoprevention with aqueous extract of Butea monosperma flowers results in normalization of nuclear morphometry and inhibition of a proliferation marker in liver tumors.

Butea monosperma (Lam.) (family: Fabaceae) popularly known as 'Palas' or 'fire of forest' has been used traditionally as a hepatoprotective agent. This study evaluated the hepatoprotective and antitumorigenic properties of the aqueous extract and butanol fractions of B. monosperma flowers in animal models. Dried flowers of B. monosperma were extracted with water and fractionated further using n-butanol. The hepatoprotective activity of the aqueous extract was initially confirmed in a carbon tetrachloride-induced liver damage model of rats. Oral administration of the aqueous extract produced a strong hepatoprotective effect similar to silymarin and normalized the serum levels of ALT, AST, bilirubin and triglyceride in rats. However, it did not affect the levels of glutathione and malondialdehyde which are oxidative stress markers in liver. Intraperitoneal administration of the aqueous extract in the X15-myc oncomice not only maintained liver architecture and nuclear morphometry but also down-regulated the serum VEGF levels. Immunohistochemical staining of liver sections with anti-Ribosomal protein S27a antibody showed post-treatment abolition of this proliferation marker from the tumor tissue. The butanol fractions, however, did not show antitumorigenic activity. Thus, the aqueous extract of B. monosperma flowers is not only hepatoprotective but also antitumorigenic by preserving the nuclear morphometry of the liver.

A clinical study of hospitalized H1N1 infected children in Western Rajasthan.

OBJECTIVE: To study the cases of H1N1 influenza admitted in our hospital. METHOD: Hospital records of all the admitted patients diagnosed as H1N1 positive by throat swab rt-PCR (real time polymerase chain reaction) were retrospectively studied. RESULTS: Between November 2009 and February 2010 total 62 children were hospitalized with 2009 H1N1 influenza virus infection. Of the admitted children, 19 (30.6%) were admitted in ICU and 4 (6.4%) expired. Consolidation was observed in 25 (40%) cases while 4 (6%) patients had pleural effusion and 1 patient each developed pneumothorax and pulmonary edema. CONCLUSIONS: Pandemic 2009 H1N1 influenza caused serious respiratory complications in children not usually seen with seasonal influenza.

Management of scorpion sting: prazosin or dobutamine.

OBJECTIVE: To compare the efficacy of Dobutamine and Prazosin in the management of cases with scorpion sting. SETTING: Pediatric intensive care unit of an affiliated hospital of a medical university. SUBJECTS: Forty-two children with scorpion sting. INTERVENTION: The involved victims were divided alternatively into two groups. Twenty-one patients were treated with intravenous Dobutamine infusion and other 21 received oral Prazosin. OUTCOME MEASURES: Percent-rise in left-ventricular ejection fraction in first 24 h after institution of the therapy, time taken in recovery from pulmonary edema, requirement of any additional drug and supportive measures, and mortality. RESULTS: The time taken in recovery from pulmonary edema was significantly shorter in cases treated with prazosin (28 +/- 18.3 vs. 72 +/- 0 h), the p-value being <0.05. Faster improvement of various parameters was observed in prazosin group in comparison to the dobutamine group. Mortality in both the groups was equal. CONCLUSION: Prazosin and dobutamine, both are useful drugs for management of cardiovascular features of scorpion envenomation, nevertheless, prazosin is slightly better than dobutamine in terms of faster recovery, and also because of its ease of administration and low cost of therapy.

Synthesis of novel steroidal D-ring substituted isoxazoline derivatives of 17-oxoandrostanes.

A facile synthesis of isoxazoline derivatives of 17-oxoandrostane at the side chain of D-ring is reported. The scheme involves the transformation of the starting dehydroepiandrosterone acetate (ketone) to the Knoevenegel product, reduction to the nitrile, and elimination to the carboxaldehyde. Cycloaddition of nitrileoxides across olefinic aldehyde intermediate led to the synthesis of novel side chain isoxazoline derivatives.

Immunomodulatory activity of biopolymeric fraction BOS 2000 from Boswellia serrata.

Oral administration of BOS 2000 (1-10 mg/kg) elicited a dose related increase in the delayed hypersensitivity reaction (early 24 h and delayed 48 h) in mice. It also stimulated the IgM and IgG titre expressed in the form of plaques (PFC) and complement fixing antibody titre. The concentration of cytokines (IL-4, IFN-gamma and TNF-alpha) in serum with respect to T cell interactions, i.e. (CD4/CD8) and the proliferation of lymphocytes were significantly increased at 10 mg/kg compared with the control. The results in these studies demonstrated the immunostimulatory effect of BOS 2000 in a dose-dependent manner with respect to the macrophage activation possibly expressing the phagocytosis and nitrite production by the enhancement of TNF-alpha and IFN-gamma production as a mode of action.

Malaria Free India - Possibility or Enigma?

Malaria, despite being treatable as well as preventable, is still quite prevalent in our country and is responsible for a large number of deaths. Though Govt. of India (GOI) has launched anti-malaria program since 1953 but is yet to achieve a zero malaria status. In SE Asia, two small countries, Maldives and Sri Lanka, have been declared Malaria free by WHO. Hence, we need to think why we cannot achieve this status? For this we need to study how these two countries were successful and what are our limitations/pitfalls. The medical profession has a great role to play. Not only we have to advise GOI to formulate the correct policy but also we need to plug the rampant pitfalls in our practice. Implementation of WHO's 3 T (Test, treat and track) policy can be a table turner.

Hemophagocytic lymphohistiocytosis presenting with acute liver failure and central nervous system involvement in early infancy.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal and likely underdiagnosed disease characterized by unregulated histiocyte proliferation, hypercytokinemia and hemophagocytosis, causing life-threatening tissue damage and organ failure. We report a case of a 56-day-old infant presenting with fever, acute liver failure, and neurological manifestations as presenting features that succumbed to rapidly progressive HLH. Our objective is to emphasize the importance of early diagnosis by high suspicion in varied initial presentation of HLH so that life-saving therapy may be instituted in time.

How to Keep a Child Healthy?

Keeping a child healthy is the most important priority of every parent. The child can be kept healthy by ensuring exclusive breastfeeding for first 6 mo of life, maintaining healthy weight throughout the childhood, providing adequate and balanced diet, promoting regular physical activity and adequate sleep, keeping a watch on all the parameters of development and referring the child to the specialist whenever deviation from normal is suspected. Proper and timely immunization as per the prevailing guidelines must be done to prevent serious infections. Stress should also be given on promoting oral as well as mental health besides other important general measures to improve the health of the child.

Synthesis and bronchodilator activity of new quinazolin derivative.

Taking lead from a naturally occurring quinazolin vasicine, a number of compounds were developed and evaluated for bronchodilator and anti-allergic activities. One of these compounds was 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino[2,1-b]quinazolin-12-one, hereinafter named 95-4, exhibited marked bronchodilator activity evaluated on contracted trachea or constricted tracheo-bronchial tree. On intestinal smooth muscle too it showed relaxant effect. Tracheal relaxant effect was not found to be mediated through beta-adrenoceptors. Cumulative dose-response study with acetylcholine and histamine indicated for its non-specific direct effect on smooth muscles. 95-4 was found to be more potent than theophylline and less to that of salbutamol on dose basis. Tested by a number of experimental models, it was found devoid of anti-allergic activity. It was also found to be free from any adverse effect. 95-4 due to its marked bronchial muscle relaxant effect can find use in conditions associated with spasm of bronchial muscles.

Profile of Kidney Histopathology in Cases of Burns - Particular Emphasis on Acridine Orange Fluorescence Study and to Explore its Forensic Utility.

INTRODUCTION: The major cause of death in the burn patients includes multiple organ failure and infection but, sometimes the exact cause of death in many fatally burned patients is difficult to detect. Many times in medico-legal post-mortem examinations in cases of burns, histopathological examination of organs is requested. AIM: The aim was to study various histopathological changes in kidneys in the post-mortem cases of burns, by using routine Haematoxylin and Eosin stain (H&E stain), special Periodic and Schiff's Stain (PAS) stain, to study the role of acridine orange fluorescence study, to explore the forensic utility of this microscopic study and to find out the relationship between duration of survival and histopathological changes observed. MATERIALS AND METHODS: An experimental longitudinal prospective study from October 2010 to September 2012. Total 32 cases of death due to burns were autopsied at mortuary, the Department of Forensic Medicine and Toxicology in our hospital. Bilateral kidneys were removed and preserved in 10% formalin solution. These were forwarded to Department of Pathology for histopathological examination. Routine microscopic examination by H&E stain as well as PAS stain and fluorescence study by acridine orange stain were done in all cases. RESULTS: It was observed that in 21 (65.63%) cases gross findings in kidneys were normal, in 06 (18.75%) were grossly pale and in 05 (15.62%) heavy & congested. Sections taken from kidneys and studied by H&E stain showed overlapping histopathological changes in all cases. In 26 (81.25%) cases, changes of Acute Tubular Necrosis (ATN) while in remaining 06 (18.75%), changes of cloudy swelling were observed. The sections stained by acridine orange and observed under fluorescent microscope were lightly positive in 15 (46.88%), brightly positive in 08 (25.00%) whereas, negative in 09 (28.12%). CONCLUSION: Microscopy by various methods helps in getting specific lesions in kidney due to burns. However, it does not add any new tool to resolve any forensic issues of burns. Therefore, microscopy (including florescent), if done would be redundant.

Renal failure in asphyxiated neonates.

A prospective case controlled study was conducted in the NICU of a tertiary level referral teaching hospital to determine the incidence of renal failure in asphyxiated neonates and to correlate severity and type of renal failure with Apgar score and hypoxic ischemic encephalopathy (HIE) grading of the neonates. Ninety-eight neonates were enrolled 70 asphyxiated babies and 28 healthy controls. Renal functions were assessed using urinary output, urine microscopy, biochemical parameters and sonographic findings. Babies having renal failure were managed on a protocolised plan and followed up till 6 months of age to detect any residual impairment. Blood urea and serum creatinine were significantly higher in asphyxiated babies compared to the control group. Biochemical derangements correlated well with HIE staging and Apgar scores. There was no significant difference in urine output in the control and the study group as significant oliguria was seen in only 7 of the 70 asphyxiated babies and the output did not correlate with severity of asphyxia. Serum sodium level and fractional excretion of sodium showed significantly different values in the asphyxiated babies compared to control. Of the 70 asphyxiated babies 33 (47.1 %) had renal failure, which was of the non-oliguric type in 78 % cases and oliguric type in 22 % cases. Sonographic abnormalities were seen more often in oliguric babies and was associated with a bad prognosis. Renal parameters normalized in all neonates by 6 months of age. Mortality was higher in babies with oliguric renal failure. We conclude that renal failure is a significant problem in asphyxiated neonates with majority of babies having nonoliguric failure. Severity of renal function abnormality correlates well with degree of asphyxia. Oliguria, hyponatremia and abnormal sonographic scan are bad prognostic signs in renal failure secondary to birth asphyxia.

A study of effect of aminoglycoside therapy on auditory brainstem evoked responses in preterm and term neonates

Background: Aminoglycosides are widely used drugs in neonates with associated ototoxic side effects, that can be diagnosed with auditory brainstem evoked responses, which is the recommended screening technique in neonatal intensive care unit infants.  This study was conducted to evaluate the effect of aminoglycoside therapy on auditory brainstem evoked responses in term and preterm neonates.Methods: A cross-sectional case control study. Two groups of 26 term and 22 preterm neonates who received aminoglycosides, with no other known risk factors for ototoxicity, were compared with suitable matched control group of 10 neonates in each. ABER was done after at least 5 days of aminoglycoside therapy and results were compared to suitable matched controls.Results: Mean latency of wave I in term neonates at 90 dB and 60 dB and mean interwave latencies of I-V waves in preterm neonates at 30 dB was higher in study group and statistically significant. No statistically significant difference in any of ABER parameters was observed in any group, at all other intensities.Conclusions: Wave I latency was prolonged in study group of term neonates at two intensities which indicates effect of aminoglycoside therapy on distal portion of acoustic nerve. But as there were no such findings at other intensities in term study group and in preterm study group and moreover no other ABER abnormalities were observed, it was concluded that the aminoglycoside therapy has low potential for ototoxicity. Authors support the ABER screening for early detection of hearing abnormalities, and recommend study on larger group of neonates and meta-analysis for final conclusion for evidence-based recommendations to use aminoglycosides in neonates, in view of audiometric and neurological abnormalities.

Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial.

PURPOSE: This study is a prospective randomized clinical trial undertaken at our center to compare low dose rate versus high dose rate intracavitary brachytherapy for the treatment of carcinoma uterine cervix. METHODS AND MATERIALS: From June 1986 to June 1989, 482 patients with previously untreated invasive squamous cell carcinoma of the uterine cervix were entered into the study. After an initial clinical examination and investigative work-up the patients were staged according to FIGO staging system. Depending upon the stage of the disease, the size of the local growth and the local cervical anatomy, the patients were divided into two main groups. In group I patients, the predominant treatment was by intracavitary therapy and in group II patients, the predominant therapy was by external beam radiation. In both the groups at the time of intracavity brachytherapy the patients were alternately randomized to receive either low dose rate or high dose rate brachytherapy. There were thus two hundred forty-six patients in the low dose rate group and two hundred thirty-six patients in the high dose rate group. The patients were analyzed for local control, 5 years survival and late radiation morbidity. RESULTS: Stage for stage the local control rates in the low dose rate group and high dose rate group were similar. The overall local control achieved in the low dose rate group was 79.7% as compared to 75.8% in the high dose rate group. The 5 years survival figures in the low dose rate and high dose rate group were also comparable. In Stage I, it was 73% for low dose rate patients and 78% for high dose rate patients, for Stage II it was 62% and 64% respectively and for Stage III patients it was 50% and 43%. The only statistically significant difference was found in the incidence of overall rectal complications which was 19.9% for the low dose rate group as compared to only 6.4% for the high dose rate group. However, the more severe grade 3-4 complications were not significantly different between the two groups (2.4% vs. 0.4%, respectively). The bladder morbidity in both the groups was similar. CONCLUSION: Thus high dose rate intracavitary brachytherapy is an equally good alternative to conventional low dose rate brachytherapy in the treatment of carcinoma of the uterine cervix.

Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata.

The diterpenes andrographolide (I), andrographiside (II) and neoandrographolide (III) isolated from Andrographis paniculata were investigated for their protective effects on hepatotoxicity induced in mice by carbon tetrachloride or tert-butylhydroperoxide (tBHP) intoxication. Pretreatment of mice with the diterpenes (I, II & III; 100 mg/kg, i.p.) for 3 consecutive days produced significant reduction in malondialdehyde formation, reduced glutathione (GSH) depletion and enzymatic leakage of glutamic-pyruvate transaminase (GPT) and alkaline phosphatase (AP) in either group of the toxin-treated animals. A comparison with the known hepatoprotective agent silymarin revealed that I exhibited a lower protective potential than II and III, which were as effective as silymarin with respect to their effects on the formation of the degradation products of lipid peroxidation and release of GPT and AP in the serum. GSH status was returned to normal only by III. The greater protective activity of II and III could be due to their glucoside groups which may act as strong antioxidants.

Incidence of human papilloma virus in patients with invasive cervical carcinoma.

The dot-blot hybridization of biotin-dUTP-labeled HPV-16 DNA with genomic DNA extracted from biopsies taken from patients with invasive carcinoma and abnormal cytology showed the presence of HPV-DNA in 88% and 80% cases under relaxed conditions and 40% and 20% cases under stringent conditions of hybridization, respectively. Southern blot revealed the HPV-DNA in randomly integrated form in two cases and in episomal form in the other two.

Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond.

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.

Anti-inflammatory activity of oleanolic acid in rats and mice.

Oleanolic acid displayed anti-inflammatory activity in carrageenan and dextran-induced oedema in rats. It elicited marked anti-arthritic action in adjuvant-induced polyarthritis in rats and mice and in formaldehyde-induced arthritis in rats. Oleanolic acid checked the inflammation-induced increased serum transaminase levels. It reduced exudate volume and inhibited leucocyte infiltration in carrageenan-induced pleurisy in rats. It is devoid of any analgesic, antipyretic or ulcerogenic action. Oleanolic acid did not affect the parturition time in pregnant rats or castor oil-induced diarrhoea in rats. Oral LD50 was found to be greater than 2 g kg-1 in mice and rats.

Evaluation of radical treatment of carcinoma esophagus using a combination of external beam and intracavitary irradiation.

Twenty five patients with squamous cell carcinoma arising from the middle third of the esophagus were treated radically, with external radiation, to a dose of 55-60 Gy. All patients had lesions less than 6 cm in length with no extra-esophageal spread on computed tomography scan. Eleven of these patients received additional intracavitary radiation to a dose of 12 Gy, 1 cm from the source axis in two sessions of 6 Gy each, a week apart. There was no significant difference in the relief of dysphagia and survival among these receiving and those not receiving intracavitary radiation. Addition of intracavitary radiation to radical external radiation was associated with significant complications like stricture and fistulae formation, which accounted for the poor results.

High dose rate intracavitary therapy in advanced carcinoma esophagus.

Nine patients with advanced squamous cell carcinoma of the middle third of the esophagus were treated by high dose rate intracavitary therapy. The dose delivered was 12 Gy in two sessions at 1 cm from the center of the source. All nine patients were alive after 9 months. Six months after treatment, 4 patients had strictures which were dilated. At the end of nine months, 6 patients had dysphagia, four of whom had strictures and two had recurrence which was treated by further intracavitary irradiation. Intracavitary radiation using high dose rate, remote controlled afterloader has a significant role in palliation in patients with advanced esophageal carcinoma and avoids intubation.