α, ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens

Dental caries and periodontal disease are associated with oral pathogens. Several plant derivatives have been evaluated with respect to their antimicrobial effects against such pathogenic microorganisms. Lippia sidoides Cham (Verbenaceae), popularly known as "Alecrim-pimenta" is a typical shrub commonly found in the Northeast of Brazil. Many plant species belonging to the genus Lippia yield very fragrant essential oils of potential economic value which are used by the industry for the commercial production of perfumes, creams, lotions, and deodorants. Since the leaves of L. sidoides are also extensively used in popular medicine for the treatment of skin wounds and cuts, the objective of the present study was to evaluate the composition and antimicrobial activity of L. sidoides essential oil. The essential oil was obtained by hydro-distillation and analyzed by GC-MS. Twelve compounds were characterized, having as major constituents thymol (56.7 percent) and carvacrol (16.7 percent). The antimicrobial activity of the oil and the major components was tested against cariogenic bacterial species of the genus Streptococcus as well as Candida albicans using the broth dilution and disk diffusion assays. The essential oil and its major components thymol and carvacrol exhibited potent antimicrobial activity against the organisms tested with minimum inhibitory concentrations ranging from 0.625 to 10.0 mg/mL. The most sensitive microorganisms were C. albicans and Streptococcus mutans. The essential oil of L. sidoides and its major components exert promising antimicrobial effects against oral pathogens and suggest its likely usefulness to combat oral microbial growth.

Leiomyoma of the kidney--report of two cases.

Renal leimyoma is an uncommon benign tumour, which pose a challenging diagnostic and therapeutic problem. When multiple (leiomyomatosis) they are preoperatively mistaken for malignant tumors. We herein-present one case of renal leiomyomatois developing in a 50 year old male, which was clinically diagnosed as renal cell carcinoma and one case of renal leiomyoma in a 37 year old male.

A new streptomycete producing diphenyl sulfone antibiotic--S. sulfonensis.

About 359 actinomycetes were isolated from 8 different natural substrates collected from different parts of Andhra Pradesh. The isolates were screened on the basis of their inhibitory effect against test organisms. Finally one potent antibiotic producer was chosen having broad-spectrum activity against Gram-positive and Gram-negative bacteria and it was found to produce a diphenyl sulfone antibiotic. On the basis of morphological, cultural, physiological and biochemical characters, the diphenyl sulfone antibiotic producer was identified as a new species and was designated as S. sulfonensis.

Traumatic transverse fracture of sacrum with cauda equina injury--a case report and review of literature.

Fractures of the sacrum are rare and generally associated with fracture of the pelvis. Transverse fractures of the sacrum are even less frequent and neurological deficit may accompany these fractures. A case of transverse fracture sacrum with cauda equina injury treated by sacral laminectomy and root decompression, is reported.

Acute myeloid leukemia in TAR syndrome.

TAR syndrome is a rare inherited autosomal recessive disorder with a mortality rate of 30-40% mainly as a result of haemorrhage, in the first year of life. Most of the infants recover from the effects of thrombocytopenia and associated haematological complications with the modern medical care. Very rarely, the outcome is fatal, with the occurrence of acute leukemias.

A new variety of Chainia olivacea from marine sediment off Gulf of Mannar.

A new variety of Chainia olivacea was isolated from marine sediment off Gulf of Mannar. The morphological, cultural, physiological and biochemical characters were studied, compared to known species and identified as a new variety of Chainia olivacea. Antibiotic activity of the strain was tested against both Gram positive and Gram negative bacteria as well as fungi and yeasts. Sodium chloride tolerance was also tested.

Incidence of primary bone tumours and tumour like lesions in and around Dakshina Kannada district of Karnataka.

A total of 523 cases of primary bone tumours and tumour like lesions in and around Dakshina Kannada district of Karnataka were diagnosed over a period of 36 years. About 39% of these tumours were malignant and the remaining benign. Among the malignant tumours the highest incidence was of osteosarcoma (45.7%) followed by Ewing's sarcoma (19.4%). Osteochondroma was the most frequent in the benign tumour category (30.3%). Peak incidence of tumour was in the 2nd and 3rd decade of life with a male preponderance. The most commonly affected bones were femur, tibia and humerus in that order. Results indicate a significantly higher incidence of primary bone tumours in this part of India.

Isolation and characterisation of bioactive actinomycetes from marine sediments.

Actinomycetes (28) were isolated from marine sediments off Madras coast by plating on Starch-Casein Agar medium. After preliminary studies, five isolates which were found to be promising were selected for detailed morphological, cultural, Physiological and biochemical studies. The genera encountered were Streptomycetes. Out of these five isolates, three isolates exhibited very good broad spectrum antibacterial activity. The sodium chloride tolerance of these five isolates was also tested.

Taurine modulates chemical nociception in mice

The effect of taurine on nociception was investigated in adult male Swiss mice using the formalin and acetic acid tests. Taurine (50-200 mg/kg) injected sc into the animals (N = 6 per group) 30 min before formalin injection into the right hind paw reduced formalin-induced early phase (0-5 min) licking activity by 30-42 per cent , but had no effect on the late phase (20-25 min) response. Writhing responses induced by acetic acid injected ip were also significantly inhibited by 49 per cent and 56 per cent by doses of 100 and 200 mg/kg taurine, respectively. In both tests taurine demonstrated antinociception which was significantly blocked by naloxone (1 mg/kg, sc, administered simultaneously with taurine). The naloxone-sensitive antinociceptive action of taurine was probably mediated via modulation of endogenous pain-regulatory systems that involve opioid peptides, neuropeptides like substance P and amino acids such as glutamate and aspartate

Possible involvement of nitric oxide in estrogen-induced uterine edema in the immature rat

We examined whether nitric oxide mediates estrogen-induced uterine edema in the immature rat. Immature Wistar rats (19-21 days) received estradiol-17 beta (E2) in a single sc dose of 10 micrograms/animal and 6 h later the animals were sacrificed and the changes in uterine wet and dry weights were determined. E2 treatment caused a 93 per cent increase in uterine wet weight (control, N = 6, 39.88 +/- 3.2 mg; E2 treated, N = 6, 76.8 +/- 4.9 mg), but not in dry weight, suggesting that it induces uterine edema. Pretreatment with L-nitroarginine methyl ester (L-NAME), a competitive antagonist of nitric oxide synthetase, at doses of 10 and 20 mg/kg, ip, caused a dose-related reduction (59 and 86 per cent ) in the uterine wet weight increase induced by E2. Furthermore, L-arginine (300-600 mg/kg, sc), the nitric oxide precursor, was able to reverse L-NAME (20 mg/kg)-induced decreases in uterine weight by 47 and 62 per cent , respectively. The results suggest that nitric oxide is the principal mediator involved in estrogen-induced uterine edema in the immature rat

Anti-anaphylactic and anti-inflammatory effects of ternatin, a flavonoid isolated from Egletes viscosa Less

Ternatin, a tetramethoxy flavone isolated from Egletes viscosa Less (Compositae), was tested for its efficacy in modulating mouse passive cutaneous anaphylaxis (PCA) and rat carrageenan-induced pleurisy. Ternatin (12.5, 25 and 50 mg/kg, ip) caused a dose-dependent inhibition of IgG antibody-mediated 1.5-h homologous PCA as well as IgE antibody-mediated 48-h homologous PCA in 2-month old mice (N = 5 per group). The inhibitory activity of ternatin was more potent on IgE-mediated PCA (47-79%) than on IgG (45-59%). In the rat carrageenan pleurisy test, ternatin (25 and 50 mg/kg, ip) reduced the response to carrageenan at 5 h both by decreasing exudate volume (33-40%) and leukocyte number (60%) in 5-6-month old rats (N = 6 per group). In contrast, indomethacin (2 mg/kg, po), a known cyclooxygenase inhibitor, showed greater potency in the inhibition of exudate volume (57%) and leukocyte number (77%). These results show that ternatin has both anti-inflammatory and anti-anaphylactic properties and suggest that it may be a useful alternative to anti-allergic drugs of the disodium cromoglycate (DSCG) type for use in bronchial asthma

Computer modelling studies of ribonuclease T1-2'-deoxy-2'-fluoroguanylyl- (3',5')-cytidine complex.

The mode of binding of the substrate analog 2'-deoxy-2'-fluoroguanylyl- (3',5')-cytidine (GfpC) to RNase T1 was determined by computer modelling studies. The results obtained are in good agreement with the observations of 1H-nmr studies. The modes of binding of the substrate analog GfpC and the substrate GpC to the enzyme RNase T1 have been compared. Though the guanine base favours to occupy the same site of the enzyme in both the complexes, significant differences are observed in the local environment around the 2'-substituent group of guanosine ribose moiety. In the RNase T1-GpC complex, the 2'-OH group is in close proximity to the side chain carboxylic acid of Glu58 which leads to the formation of a hydrogen bond. However, in the RNase T1-GfpC complex, 2'-fluorine is positioned away from Glu58 due to electrostatic repulsion and instead forms a hydrogen bond with His40 imidazolium group. The results obtained rule out the possibility of His40 serving as the base group in catalysis as suggested by 1H-nmr studies and further support the primary role assigned to Glu58 as the general base group by earlier computer modelling and the recent site directed mutagenesis studies. This study also implies that the 2'-deoxy-2'-fluoro substrate analog may not serve as a good model for determining the amino acid residue which serves as the general base group in ribonuclease catalysed reactions.

Involvement of PAF-acether and eicosanoids in adrenaline-induced pulmonary edema in mice

The participation of platelet-activating factor (PAF,PAF-acether) in a mouse model of pulmonary edema was studied using specific antagonists.Mice were treated before induction of edema with the PAF antagonists BN52021 (10mg/kg, ip), PCA 4248 (10 mg/kg, po) or WEB2170 (10mg/kg, ip),the lipoxygenase inhibitor EP10161 (10 mg/kg,ip),the cyclo-oxygenase inhibitor aspirin (250 mg/kg,po), or with the mixed cyclo-lipoxygenase inhibitor BW755C(50 mg/kg, ip).The test drugs were administered to animals either 30 min (When the ip route was used) or 60 min (when given po) prior to the induction of pulmonary edema.Pulmonary edema was induced by intravenous administration of adrenaline (2 mg/kg). When the lung-body index was usedas thecriterion for comparision between groups,BN52021, PCA4248 and WEB2170 were found to have no significant effect on pulmonary edema. In contrast, EP10161, aspirinand BW755C significantly inhibited pulmonary edemaby 49%,30% and 27%,respectively. The results suggest that arachidonate metabolites are likely to play a major roe in adrenaline-induced pulmonary edema in mice, whereas PAF-acether does not seem to play an important role in this model

Evaluation of the purified fraction of Wilbrandia (c. f. ) verticillata for antitumour activity

Cucurbatacins are known to produce cytotoxic and anticancer activities. Two novel norcucurbitacin glucosides (Wvl and Wv2) have recently been isolated from a purified fraction obtained from the rhizome of Wilbrandia verticillata. The present study evaluates the cytotoxic and anti-tumour activities of the norcucurbitacins. We have found a regular cytotoxicity in KB cells (Cy50 = 12µg/ml) as well as a significant inhibition in the Walker 256 carcinosarcoma growth (approximately 75%).

Pharmacological and toxicological evaluation of Alpinia speciosa

Alpinia speciosa Schum or A. nutans is a plant of the Zingiberanceae family, Known popularly as "colony" (colônia) and used as a diuretic and to control hypertensión. We have determinated the concentration of Na+ and K+ found in the alcoholic extract and in the tea concoction. They contained 51.0mEq Na+, and 132 mEq K+ in the extract, and 0,0 mEq of Na+ and 26 mEq K+ in the tea. Phytochemical analysis of the leaves demonstrated the presence of catecquic tanins, phenols and alkaloids, and also some essential oils. When injected intra-peritoneally the hydroalcoholic extract, in range of 100 a 1400 mg/Kg, (or 2500-18000 mg/Kg orally) produced in mice: writhing, psychomorot excitation, hypokinesis and pruritus. The LD50 by ip was 0.760 + or - 0.126 g/Kg and 10.0 + or - 2.5 g/Kg by oral administration for the hydroalcoholic extract. Subacute toxicity made injecting daily for 30 days the LD10 in rats caused an increase in transaminases and lactate dehydrogenase, whereas other parameters such as nlood glucose, urea and creatinine were normal. A histopathological analysis of liver, spleen, gut, lung and heart showed no alterations. The drug also produced a prolongation of the sleeping time. The hydroalcoholic extract induced int he rat and in the dog a dose-dependent fall in blood pressure in doses of 10 to 30 mg/Kg. In isolated atria the extract induced a reduction of the frequnecy and in the inotropic responses. Neither the extract nor the tea had an effect on the diuresis of the rat.

Efficacy of two different DEC regimens in the treatment of human filarial infection.

Two regimens of diethyl carbamazine (DEC) viz., 14 day and 5 day, were compared for microfilaricidal effect and side effects, in the treatment of bancroftian filariasis. The rate of successful treatment, cure rate and decrease in mf count were found to be significantly high with the 14 days regimen when assessed immediately after treatment. About 40 per cent of subjects on the 14 days regimen and 66 per cent of patients on 5 days regimen experienced side reactions. The severity of side reactions was more in patients on 5 days regimen. When the effect of DEC was assessed one year after treatment with the 14 days regimen and compared with the results immediately after treatment, the rate of successful treatment, cure rate and decrease in mf count were reduced significantly. The 14 days DEC regimen with initial low dose of DEC along with antipyretics may be better accepted in the control programmes of filariasis.

Inhibition of formaldehyde-induced arthritis by a purified fraction prepared from Wilbrandia (cf) verticillata which contains novel norcucurbitacin glucosides

The anti-inflammatory activity of a purified fraction of the rhizome of Wilbrandia (cf) verticillata, which contains two novel norcucurbitacin glucosides, is reported. The increase of vascular permeability induced by acetic acid in mice (N = 5) was inhibited 69% and 90% by 50 and 100 mg/kg of the purified fraction, po (P<0.01). Acetylsalicylic acid (200 mg/kg), po, inhibited the response by 62% under the same conditions (P<0.05). The purified fraction (100 mg/kg, po) also significantly inhibited paw swelling in the rat formaldehyde-induced arthritis model on 8 of 10 days and reduced the swelling by 63% on day 10. Dexamethasone (1 mg/kg, ip) was more effective than the extract under the same conditions. These data partially characterize the anti-inflammatory activity of the purified fraction from this plant which is used in Brazilian folk medicine for the treatment of arthritis and related disorders

Effect of Astronium urundeuva (aroeira) on gastrointestinal transit in mice

In order to assess the use of Astronium urundeuva in folk medicine for treatment of diarrheal conditions, the alcoholic extract of its bark was tested on gastrointestinal transit in mice. The extract at oral doses of 100 and 200 mg/kg significantly inhibited physostigmine-induced gastrointestinal propulsion. Considering these data together with an in-vitro anti-acetylcholine effect reported earlier from this laboratory, we suggest that anti-cholinergic effects of the plant may account in part for its anti-diarrheal activity