On valorization of solvent extracts of Terminalia arjuna (arjuna) upon DNA scission and free radical scavenging improves coupling responses and cognitive functions under in vitro conditions.

Chronic diseases have been treated using the phytochemical concepts of ethnomedicinal plant-derived herbal products. Terminalia arjuna, a significant ethnomedicinal plant, was revisited and reconnoitred for antioxidant, free radical scavenging, and DNA nicking inhibiting activity under H2O2 conditions using 21 solvent extracts. Ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and nitrous oxide scavenging (%) were found to have a strong positive association and interaction (PCA 1 explains 84.54% variation) with ethanol bark (Etoh-AB) (Meoh-AF). TPC (144.67-1794 µg/mL GAE) and TFC (2.5-34 µM Fe(II)/g were highest in Etoh-AB. In a pattern of combined solvent extracts, Etoh-AB had the highest antioxidant capacity, accompanied by Etoh-AL ≥ Meoh-AB ≥ Dw-AF. With R2 = 0.94, the DNA nicking inhibition behaviour parameters relative front, relative quantity, band (%), and lane (%) formed a positive significant (p < 0.01) connection. For the first time, we show that Etoh-AB nicks supercoiled, circular plasmid DNA in a way that is comparable to normal antioxidants. Normal antioxidants with the ability to prevent DNA nicking include Butylated hydroxy anisole < Butylated hydroxy toluene < ascorbic acid < and Gallic acid. Gallic acid (m/z 170.0208 g/mol) and Ellagic acid (m/z 302.0063 g/mol were present in high concentrations in solvent extracts. 0.48 mg was found to be the effective concentration for inhibiting relative DNA nicking. The current study is the first of its kind to show that steroid concentrations are higher in bark fractions of acetone, ethanol, and methanol. Furthermore, T. arjuna solvent extracts provide a wealth of information on phytochemical profiling, antioxidant ability, and DNA nicking inhibition, which may be useful for exploring the natural way and further research to develop a remedy against geriatric chronic disease. Despite the fact that ethanol is very close to methanol in terms of solvent toxicity, the current study identified it as the preferred solvent. Thus, the current research revisits previous studies and explores the potentiality of non-polar and polar aprotic and polar protic solvent systems, which lend credence to bioactive compounds that may be useful in isolating and formulating safe and cost effective herbal medicament for livestocks and aquaculture, and drugs for deoxygenerative human diseases, and can also be investigated further to instil environmental frugality.

Molecular characterization of group A rotavirus (RVA) strains detected in bovine and porcine species: Circulation of unusual rotavirus strains. A study from western, India.

Group A rotaviruses (RVA) are considered as important causative agents of diarrhea in both human and animal species. Fecal specimens (n = 300) were collected from both diarrheic and healthy animals during the year 2009 from animal farms from Nagpur (Maharashtra), Western India. RVA antigen was detected by ELISA in 3.1-25% and 72% in bovine and porcine species, respectively. Genotyping based on VP6, VP7 and VP4 of RVA-positive samples showed predominance of genotype I-1 (63%) and genotype I-2 (37%), G4 (45.5%) and G10 (27.3%) genotypes, P[6] (72.7%) and P[8] (18.1%) genotypes, respectively. Other RV genotypes such as G1(4.5%), G2(9.1%), G3(4.5%) and mixed infections (9.1%) were detected at low level. Predominance of unusual G-P combinations (9/23, 39.1%) were observed. Circulation of G2P[8] and mixed infections with G1, G3, P[6] and G1, P[8], P[6]) are reported in porcine species for the first time in Western India. In conclusion the present study highlights the circulation of unusual G-P combinations and VP6 genogroup specificities of human RVA strains indicative of possible interspecies transmission and reassortment events in animal species. The study further warrants utmost need for such surveillance studies across the country to understand the role of animals as genetic reservoirs for the emergence of RVA strains pathogenic for humans. Keywords: rotaviruses; genotypes; unusual G-P types; animals.

An Innovative Method to Determine the Width of Maxillary Anterior Teeth with the Help of Measurements Obtained from the Master Cast.

AIM: Analyse the correlation between the measurements made from the landmarks on the cast and the width of the anterior teeth in dentulous study subjects and assessed whether a similar correlation exists in edentulous condition. MATERIALS AND METHODS: Measurements were made on the cast of dentulous and edentulous subjects. The measurements made were, from incisive papilla to the right hamular notch, from incisiv e papilla to left hamular notch and distance between two hamular notches. After measuring these distances, the predicted value was calculated by taking mean of these three distances. The actual value in both the groups was measured with a flexible ruler. The mean and standard deviation of both groups were calculated. Results were analyzed with correlation and regression analysis. RESULTS: The analysis showed that there was a positive correlation between actual and predicted values in both dentulous and edentulous group of study subjects (p-value <0.01). As the actual value increased in both the groups, the predicted value also increased. So the actual value can be derived with the help of predicted value which will be useful in selecting the proper tooth mold size of the maxillary teeth for edentulous patients. CONCLUSION: A positive correlation exists between the width of the maxillary teeth (actual value) and mean of the distance (predicted value) between the right hamular notch and incisive papilla, left hamular notch and incisive papilla and interhamular distance in dentate subjects. CLINICAL SIGNIFICANCE: The results obtained from the present study will be helpful for selecting the proper teeth mold size along with other teeth selection methods. Further studies are required to derive a more scientific and reliable method for anterior teeth selection.

A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India.

BACKGROUND: In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. MATERIALS AND METHODS: A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. RESULTS: The average body weight of patients was 26.4 ± 14.8 (n=22), 32.9 ± 19.4 (n=23) and 37.9 ± 20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2 ± 13.4, 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8, 16.2 ± 8.3, and 14.7 ± 10.7 days, respectively. The time to resolve fever was 13.3 ± 10.2, 10.9 ± 7.1, 10.1 ± 6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4 ± 9.6, 10.6 ± 7.6 and 7.3 ± 3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS: This small randomized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

Aliskiren, the first direct renin inhibitor for treatment of hypertension: the path of its development.

Standard treatments available today for treating hypertension is diuretics, ß-blockers, angiotensin converting enzyme inhibitors (ACEs), angiotensin receptor blockers (ARBs), calcium channel blockers, a-blockers, vasodilators, and centrally acting drugs. It is difficult to achieve the optimized renin angiotensin aldosterone system suppression with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate the compensatory feedback mechanism that increases renin release and increase plasma renin activity. The first orally active direct renin inhibitors (DRIs) were developed in 1980s, including enalkiren, remikiren, and zankiren. However, poor absorption from the gastrointestinal tract, less bioavailability (<2%), short half life, and low potency hindered the development of these compounds. Aliskiren is the first DRI for the treatment of hypertension. Aliskiren is designed through a combination of molecular modeling techniques and crystal structure elucidation. Aliskiren effectively reduces the blood pressure as a mono therapy as well in combination therapy.

Formulation and Evaluation of Long Circulating Liposomal Amphotericin B: A Scinti-kinetic Study using Tc in BALB/C Mice.

In the present study, we formulated long circulating liposomes for amphotericin B and characterized them. The formulation was optimized using 2(3) factorial designs. Pegylated liposomal formulation showed favorable results with reference to particle size (247.33±9.60 nm), percent entrapment efficiency (94.55±3.34%). TEM studies revealed that the liposomes were essentially spherical, hollow, and appeared like powder puff structures. From DSC study it was concluded that the pegylated formulation containing Amp B showed better stability and membrane integrity of the formulation. During the stability studies the formulation was found to be stable. When subjected to gamma scintigraphy kinetic tracer studies the formulation showed longer residence time in the blood in BALB/C mice.

Assessment of use of complementary alternative medicine and its impact on quality of life in the patients attending rheumatology clinic, in a tertiary care centre in India.

PURPOSE: Complementary and alternative medicine (CAM) has witnessed an increase in use in recent times in rheumatological conditions and is expected to have impact on the quality of life (QOL). We had planned to conduct this study to investigate the extent of use of CAM and its effect on QOL of patients at a tertiary care center. MATERIALS AND METHODS: Ethics committee approval was obtained. Sixty patients suffering from osteoarthritis (OA) and rheumatoid arthritis (RA) were enrolled as per the selection criteria, after obtaining their informed consent. Each patient was interviewed for CAM use/non-use, and Western Ontario and McMaster Universities (WOMAC) (modified) index for QOL was recorded by the study personnel. STATISTICAL ANALYSIS: The normality was checked by using Kolmogorov-Smirnov test. Descriptive statistics was performed and Mann-Whitney U-test was used to compare the QOL of CAM users and non-users. RESULTS: Of the 60 patients enrolled with OA (10) and RA (50), 58% (35/60) used CAM. Ayurveda and massage therapy were the commonest [80% (28/35)], followed by yoga asana [34% (12/35)] and homoeopathy [20% (7/35)]. It was observed that combinations of therapies were used too. Nearly half [49% (17/35)] of the CAM users were on self-prescribed medication and 71% (25/35) of them did not inform the physician of CAM use. The QOL of CAM users (WOMAC score: 56.31 ± 6.82) was better than that of CAM non-users (WOMAC score: 60.16 ± 4.02) (P value 0.01). CONCLUSION: Patients with RA frequently used CAM and QOL improvised with CAM use. We observed that self-administration of CAM was common and this was not informed to the treating physician.

Liposomal amphotericin B (Fungisome) for the treatment of cryptococcal meningitis in HIV/AIDS patients in India: a multicentric, randomized controlled trial.

BACKGROUND: There is need to investigate the use of liposomal amphotericin B in cryptococcal meningitis in India. AIMS: To compare the efficacy, safety, duration of treatment and cost of two doses of liposomal amphotericin B (Amp B) (Fungisome) in cryptococcal meningitis in HIV/AIDS patients. SETTINGS AND DESIGN: Prospective, randomized, multicenter study in tertiary care hospitals across India. MATERIALS AND METHODS: Adult patients with culture-proven cryptococcal meningitis with HIV/AIDS were randomized to receive either 1 (Group A) or 3 mg/kg/day of Fungisome (Group B). Clinical efficacy and tolerability, laboratory evaluations and mycological response were assessed daily, twice weekly and weekly respectively. The patients were assessed at four and eight-week follow-up. STATISTICS: We calculated average and standard deviation for the various parameters. RESULTS: The time to show clinical response was 13.66 days (1 mg) and 9.55 days (3 mg). In Group B (n=6 complete response), 50% patients responded within one week by microbial conversion, 83% in two weeks and 100% in three weeks. Patients with 1 mg dose (n=4 complete response), none showed microbial conversion within one week, 75% responded in two weeks, whereas one patient took four weeks. The average duration of treatment was 36.5+/-14.4 and 26.5+/-5.89 (S.D.) days in 1 and 3 mg/kg/day respectively. Drug was tolerated with little renal, hepatic or hematological toxicity. The cost was found to be 3.81 lacs and 1.74 lacs with 3mg/kg/day and 1mg/kg/day respectively. CONCLUSION: Higher dose showed better efficacy and quicker microbial conversion of Cerebrospinal fluid (CSF) (cerebrospinal fluid) than 1 mg/kg/day. It shortened the duration of treatment in days by 27% while drug cost almost doubled ( CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN 52812742).

Disseminated histoplamosis.

A case of disseminated histoplasmosis in a 45-year-old male patient with acquired immunodeficiency syndrome (AIDS) from Pune is reported. The patient presented with high-grade fever and pain in hypochondrium. Clinical signs were pallor and hepatosplenomegaly. Bone marrow and splenic aspirate revealed numerous intracellular oval shaped yeast forms. Histoplasma capsulatum was isolated from the bone marrow and splenic aspirate. H. capsulatum infection is an opportunistic infection usually reported from patient with AIDS in areas endemic for H. capsulatum. The present case highlights the fact that histoplasmosis could be an emerging opportunistic infection in India.

A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

76 skin biopsies that included material from 7 controls, 65 granulomatous skin lesions and 2 each of granulation tissue and chronic non-specific inflammation, were subjected to histopathological evaluation on haematoxylin and eosin and pertinent special stains. Mast cell study was done on slides stained by toluidine blue method, with special reference to their location, and morphology and cell count were done with the help of occculomicrometre. In normal skin, mast cell density was 11.43/mm2 with a range of 6-22/mm2 and an S.D. of 5.94. Highest value in the whole series was seen in TVC (66/mm2), followed by lupus vulgaris (50/mm2). Mast cell counts were normal in indeterminate and TT leprosy and showed a rise over the immunological spectrum BT to LL, with values in LL being 32.86/mm2 (28-40/mm2).

Tissue concentration, systemic distribution and toxicity of clofazimine--an autopsy study.

There are very few autopsy studies available on systemic distribution of clofazimine, a drug with anti-mycobacterial activity, used in multidrug therapy (MDT) regimen of leprosy and in erythema nodosum leprosum (ENL). An autopsy study was done on a 45 year old female of lepromatous leprosy (LL) on MDT and long term high dosage of clofazimine. Patient succumbed to intractable abdominal pain, diarrhoea, hypokalemia following clofazimine treatment. Autopsy study revealed yellowish brown discoloration of skin, viscera and body fluids. Chemical extraction of the drug revealed the highest concentration of the drug in jejunum (1.5mg/gm),followed by spleen (1.2mg/gm), pancreas (0.4mg/gm), adrenal (0.25mg/gm), liver (0.21mg/gm), and less than 0.2mg/gm in lung, fat, large intestine and stomach. It can be inferred from the present study that the drug is absorbed from the jejunum and gets deposited in fat, reticulo-endothelial cells (R-E cells) and hepatocytes. The drug is best demonstrated in cryostat sections and is lost partly during tissue processing and staining. The drug toxicity can be fatal as seen in the present case.

Autopsy study of maternal deaths.

OBJECTIVES: To obtain an insight into the underlying disorder or pathologies in different organs or systems, and to attempt clinicopathologic correlation in maternal deaths. METHODS: This is a retrospective study of 95 maternal autopsies done from 1993 to 2000 in Sassoon General Hospital, Pune, India. External examination, in situ examination, gross and microscopic examination was done in each case. The cause of death was arrived at after reviewing clinical details, available investigations, morphological findings, and clinicopathologic correlation. RESULTS: Ninety-five (45.02%) out of 211 maternal deaths were autopsied. Out of 95, there were 47 (49.5%) direct obstetric deaths, and 33 (34.7%) indirect obstetric deaths. Fifteen (15.8%) deaths were unrelated to pregnancy, 14 of which were due to infections. CONCLUSIONS: Hypertensive disorders associated with pregnancy (24.2%) and anemia (14.7%) were most common. In the hypertensive group, important findings were disseminated intravascular coagulation, hemorrhages in different organs and thromboemboli. Two cases were HIV seropositive. The autopsy helped to elucidate factors contributing to death and pathology in different organ systems.

Pathology of Toxoplasma myocarditis in acquired immunodeficiency syndrome.

Involvement of the myocardium by Toxoplasma gondii is seen in patients of acquired immunodeficiency syndrome (AIDS), mostly in association with toxoplasma encephalitis. Only few patients die as a direct result of cardiac dysfunction. Clinico-pathological findings of three cases of toxoplasma myocarditis are reported, one of which presented and died due to massive pericardial effusion. All cases showed diffuse myocarditis with parasites on histopathological examination. Incidence of toxoplasma myocarditis in patients dying with AIDS was 8.3% (3 out of 36 cases).

Effects of niosomal cisplatin and combination of the same with theophylline and with activated macrophages in murine B16F10 melanoma model.

The use of cisplatin is limited due to its certain toxic effects. In the present study niosomes of cisplatin by using span 60 and cholesterol were prepared and investigated for antimetastatic activity in experimental metastatic model of B16F10 melanoma. Theophylline and its combination effect with free cisplatin and niosomal cisplatin were also carried out in the same model. The effect of treatment with activated macrophages alone and in combination with cisplatin, theophylline and niosomal cisplatin was also observed. Treatment with niosomal cisplatin (1 mg/kg) and combination of the same with theophylline (15 mg/kg) showed significant reduction in the number of lung nodules as compared to untreated control as well as with free cisplatin (1 mg/kg). The treatment with activated macrophages (activated by using Muramyl dipeptide) significantly reduced the secondary growth of tumor in lung. Niosomal cisplatin showed a significant protection against weight loss and bone marrow toxicity as compared to free cisplatin. These results suggest that cisplatin encapsulated in niosomes has significant antimetastatic activity and reduced toxicities than that of free cisplatin. However theophylline failed to show antimetastatic effect alone or in combination with cisplatin or with activated macrophages.

Autopsy study of pediatric deaths.

OBJECTIVE: Childhood autopsies occurring during January 1997 to December 1999 were reviewed. METHOD: Of the total 1,445 deaths autopsied, 441 (30.5%) were of pediatric patients. RESULT: Of these deaths, 70.3% occurred during neonatal period, 8.6% in infancy, and 21.1% in childhood. Birth asphyxia (57.7%) was the most frequent mode of death in the neonatal period. Infections (67.2%) predominantly accounted for infant and childhood mortality, those of respiratory tract (46.1%) being most frequent in infancy, early and mid childhood, and enteric fever in late childhood (33.3%). Discrepancy between ante-mortem and post-mortem diagnosis occurred in 29 cases (6.6%). CONCLUSION: Autopsy is an important clinical tool providing useful information to the physician. Few published reports are available on pediatric autopsies. This study aims to help in a better understanding of causes of deaths in neonates, infants and children.

Dedifferentiated chordoma--a case report.

A case of a recurrent sacro-coccygeal chordoma is reported which histologically showed an admixture of a conventional chordoma and a pleomorphic sarcoma. These tumours are called dedifferentiated chordomas and carry an ominous prognosis.

Protein profile in leprosy.

Serum proteins and plasma fibrinogen were estimated in 103 patients in various groups of leprosy and 52 patients of reactional leprosy. Total proteins, serum globulin and fibrinogen showed significant rise while serum albumin showed fall over the immunological spectrum from TT to LL. Type II reactional leprosy similarly revealed significant rise in globulin and fibrinogen. The comparison of these parameters between most of the comparable groups of leprosy was statistically significant. ENL patients after complete subsidence of reaction and after steroid treatment showed significant decrease in these protein fractions, thus conferring some prognostic implication on these tests.