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.

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.

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.

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.

A comparative study of microscopic images captured by a box type digital camera versus a standard microscopic photography camera unit.

INTRODUCTION: Obtaining images of slides viewed by a microscope can be invaluable for both diagnosis and teaching.They can be transferred among technologically-advanced hospitals for further consultation and evaluation. But a standard microscopic photography camera unit (MPCU)(MIPS-Microscopic Image projection System) is costly and not available in resource poor settings. The aim of our endeavour was to find a comparable and cheaper alternative method for photomicrography. MATERIALS AND METHODS: We used a NIKON Coolpix S6150 camera (box type digital camera) with Olympus CH20i microscope and a fluorescent microscope for the purpose of this study. RESULTS: We got comparable results for capturing images of light microscopy, but the results were not as satisfactory for fluorescent microscopy. CONCLUSION: A box type digital camera is a comparable, less expensive and convenient alternative to microscopic photography camera unit.

Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin.

In the present study, novel spiro derivatives of α-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of α-santonin (α-methylene-γ-butyrolactone) by the 1,3-dipolar cycloaddition of α-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b″ had shown IC50 of 0.01, 0.5 and 0.3 µM against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b″ were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b″ also showed concentration dependent inhibitory activity against NF-κB, p65 with 57% inhibition in 24 h at 10 µM.

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.

Epibrassinolide ameliorates Cr (VI) stress via influencing the levels of indole-3-acetic acid, abscisic acid, polyamines and antioxidant system of radish seedlings.

The present investigation determined the effects of epibrassinolide (EBL) on the levels of indole-3-acetic acid (IAA), abscisic acid (ABA), and polyamine (PA) and antioxidant potential of 7-d old Raphanus sativus L. cv. 'Pusa chetki' seedlings grown under Cr (VI) metal stress. Reduced titers of free (0.767 µg g(-1) FW) and bound (0.545 µg g(-1) FW) IAA in Cr (VI) stressed seedlings were observed over untreated control. Supplementations of EBL to Cr (VI) stressed seedlings were able to enhance both free (2.14-5.68 µg g(-1) FW) and bound IAA (2.45-7.78 µg g(-1) FW) concentrations in comparison to Cr (VI) metal treatment alone. Significant rise in free (13.49 µg g(-1) FW) and bound (12.17 µg g(-1) FW) ABA contents were noticed for Cr (VI) stressed seedlings when compared to untreated control. No significant increase in ABA contents were recorded for Cr (VI) stressed seedlings upon supplementation with EBL over Cr (VI) treatment alone. A significant increase in Put (18.40 µg g(-1) FW) and Cad (9.08 µg g(-1) FW) contents were found for 10(-9)M EBL plus Cr (VI) metal treatments when compared to Cr (VI) treatment alone. Spermidine (Spd) contents were found to decline significantly for EBL treatment alone or when supplemented with Cr (VI) treatments over untreated controls and Cr (VI) treatment alone. Antioxidant levels were found to enhance, with glutathione (57.98 mg g(-1) FW), proline (4.97 mg g(-1) FW), glycinebetaine (39.01 µmol mL(-1)), ascorbic acid (3.17 mg g(-1) FW) and phytochelatins (65.69 µmol g(-1) FW) contents noted for EBL supplemented to Cr (VI) metal solution over Cr (VI) treatment alone. Reduced activities of guaiacol peroxidase (0.391 U mg(-1) protein) and catalase (0.221 U mg(-1) protein) and enhanced activities of glutathione reductase (7.14 U mg(-1) protein), superoxide dismutase (15.20 U mg(-1) protein) and ascorbate peroxidase (4.31 U mg(-1) protein) were observed in seedlings treated with EBL plus Cr (VI) over Cr metal treatment alone. Reduced MDA (2.55 µmol g(-1) FW) and H(2)O(2) (33.24 µmol g(-1) FW) contents were recorded for 10(-9)M EBL supplemented to Cr (VI) stress over Cr (VI) treatment alone. Enhancement in free radical scavenging potential as indicated by higher values of 1,1-diphenylpicrylhydrazyl, deoxyribose and reducing power activity assays, and increased levels of phenols and soluble sugars also showed significant influence of EBL in alleviating Cr (VI) stress in radish seedlings.

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.

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.

D-ring substituted 1,2,3-triazolyl 20-keto pregnenanes as potential anticancer agents: Synthesis and biological evaluation.

A facile synthesis of 21-triazolyl derivatives of pregnenolone and their potential antitumour activity is reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to 21-bromo pregnenolone and finally the one-pot, two-step in situ conversion of the bromo derivative to the 21-triazolyl pregnenolone using the 'click chemistry' approach. These derivatives were screened for their anticancer activity against seven human cancer cell lines. The compounds especially 5a, 5b, 5c, 5e, 5g and 5h exhibited significant anticancer activity with compound 5e as the most active in this study.

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.

Pharmacokinetic interaction of some antitubercular drugs with caraway: implications in the enhancement of drug bioavailability.

This study deals with the pharmacokinetic interaction of selected anti-TB drugs with a natural product (CC-1a) derived from caraway (Carum carvi, L.) seed. CC-1a, chemically standardized butanolic fraction, enhanced the plasma levels of rifampicin, pyrazinamide, and isoniazid in Wistar rat, resulting in increased bioavailability indices (C(max) and AUC) of the drugs. Moreover, a 40% reduced dose regimen of these drugs, which additionally contained CC-1a, was equivalent in terms of C(max) and AUC to a normal dose regimen. A permeation-enhancing property of CC-1a across small intestinal absorptive surface was found to be a contributing factor in its bioavailability enhancing profile.

Anti-allergic effects of herbal product from Allium cepa (bulb).

Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

A unique trend of murder-suicide in the Jamnagar region of Gujarat, India (a retrospective study of 5 years).

Jamnagar region, Gujarat state, enjoys a relatively low incidence of homicide in India. In the 5 year period from 2000 to 2004, 8 mothers committed 13 murders involving 3 male and 10 female victims and in every case it was followed by suicide of the assailant mothers. During the study the annual incidence of murder-suicide was about 1.8 cases. All the assailants were mothers and the victims were their small children in the age group of 6 months to 7 years. Five incidents took place in rural areas and three in urban areas. It was prevalent only in low socio-economic families. Methods both for killing and suicide were either burning or drowning. All the mothers were legally married and living with the family. Family and family related matters were the main motives for killing. In one case there was history of depression of the mother due to her previous miscarriage. Alcohol consumption or drug abuse was not seen even in a single case. All cases fell in the altruistic category of filicide-suicide.

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.

A new vaccine adjuvant (BOS 2000) a potent enhancer mixed Th1/Th2 immune responses in mice immunized with HBsAg.

Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component. In search of a potent vaccine adjuvant, the water-soluble biopolymeric fraction BOS 2000 from Boswellia serrata was evaluated for desired activity. We investigated the ability of BOS 2000 to enhance HBsAg specific immune responses. The effect was determined in the form of protective anti-HBsAg titers, neutralizing antibodies (IgG1 and IgG2a), spleen cell lymphocyte proliferation by using MTT assay, Th1 (IFN-gamma and TNF-alpha) and Th2 (IL-4) cytokines as well as T-lymphocyte subsets (CD4/CD8) and intracellular cytokines (IFN-gamma/IL-4), these responses were highest in BOS 2000 immunized mice. Alum induced only a modest enhancement of antibody responses. Reducing the dose of adjuvant by 18.1-fold in comparison to alum, total IgG and its subtypes (IgG1 and IgG2a) antibodies titer in serum was significantly enhanced. Analysis of HBsAg specific cytokines revealed that alum was associated with a predominantly IL-4 response. In contrast, BOS 2000 was associated with production of both IFN-gamma and IL-4. We conclude that BOS 2000 is a potent enhancer of antigen-specific Th1 and Th2 immune responses in comparison to alum with Th2 limitation and is a promising adjuvant for vaccine applications.

Herbal modulation of drug bioavailability: enhancement of rifampicin levels in plasma by herbal products and a flavonoid glycoside derived from Cuminum cyminum.

The bioavailability of rifampicin (RIF) in a fixed dose combination (FDC) used for the treatment of tuberculosis remains an area of clinical concern and several pharmaceutical alternatives are being explored to overcome this problem. The present study presents a pharmacological approach in which the bioavailability of a drug may be modulated by utilizing the herb-drug synergism. The pharmacokinetic interaction of some herbal products and a pure molecule isolated from Cuminum cyminum with RIF is shown in this paper. An aqueous extract derived from cumin seeds produced a significant enhancement of RIF levels in rat plasma. This activity was found to be due to a flavonoid glycoside, 3',5-dihydroxyflavone 7-O-beta-D-galacturonide 4'-O-beta-D-glucopyranoside (CC-I). CC-I enhanced the Cmax by 35% and AUC by 53% of RIF. The altered bioavailability profile of RIF could be attributed to a permeation enhancing effect of this glycoside.