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Biomedical subjects

A Gomes

Publications and source records attributed to A Gomes.

At least 37 records · Page 2Linked to original sources

Antineoplastic effect of new boron compounds against leukemic cell lines and cells from leukemic patients.

Three new boron compounds, dihydroxy (oxybiguanido) boron (iii) hydrochloride monohydrate (HB), guanidine biboric acid adduct (GB) and hydroxosalicyl hydroxomato boron (iii) (SHB) were studied to observe their antineoplastic effect, if any. Leukemic cells isolated from acute lymphatic leukaemia (ALL) patients and chronic myeloid leukaemia patients (CML) and myeloid leukemia cell lines (HL 60 and U-937) showed cell growth inhibition after treatment with the boron compounds. MTT assay showed that the growth of metabolically active cells was inhibited by treatment with these drugs. The molecular mechanism by which SHB induced apoptosis in immature blast cells was also investigated by ladder formation in gel electrophoresis.

Acute Disease↗

Pharmacological and haematological study of shol fish (Channa striatus) skin extract on experimental animal.

Snake head fish Channa striatus (locally called 'shol') skin extract (SFSE) was examined for certain pharmacological and haematological effects on experimental animals. LD50 of SFSE was found to be 6 mg/20gm (iv) in male albino mice. SFSE potentiated pentobarbitone induced sleeping time in male albino mice and produced hypothermia. Low dose of SFSE decreased respiratory rate in rat and guineapig and high dose produced apnoea leading to death. On isolated toad and guineapig heart, SFSE significantly decreased rate and amplitude of contraction leading to temporary blockade, which returned after repeated wash. On isolated nerve muscle preparations, SFSE produced irreversible blockade of twitch response. SFSE induced quick contraction on isolated guineapig ileum, which was antagonised by atropine and cyproheptadine. SFSE did not possess haemolytic and haemorrhagic activity but produced anaemia in male albino mice. A neurotoxic compound (fluoroscent and ninhydrin positive) was isolated from SFSE by thin layer chromatography. This compound (CS-NT) was lethal in male albino mice, produced death by apnoea in rat and produced irreversible blockade of isolated nerve-muscle preparation. This study confirms that the skin of Channa striatus possesses toxic, and lethal components, which needs further detailed study.

Anemia↗

Studies with black tea and its constituents on leukemic cells and cell lines.

The anticancer effect of black tea (BT) and its polyphenols theaflavin (TF) and thearubigin (TR) has been evaluated on U-937 cell line, a myeloid leukemic cell line and on leukemic cells isolated from peripheral blood of chronic myeloid leukemia (CML) patients. In both types of cells, cell growth inhibition was observed 24 hrs after treatment with BT, TF and TR. MTT assay showed growth inhibition of metabolically active cells and inhibition of DNA synthesis was observed by 3H-Thymidine incorporation after treatment with the compounds. In all cases TF and TR were more effective than BT, suggesting that these are possibly the active components in BT responsible for its antileukemic activity. Superoxide dismutase (SOD), a free radical scavenger, was found to be increased by TF, whereas BT and TR lowered the level in comparison to the control. The present study is the first report of antileukemic effect of BT and its polyphenols.

Anticarcinogenic Agents↗

A lethal neurotoxic protein from Indian king cobra (Ophiophagus hannah) venom.

A lethal neurotoxin protein (Toxin CM36) was isolated and purified from the Indian King Cobra (Ophiophagus hannah) venom by CM-Sephadex ion exchange chromatography and HPLC. The purified toxin had a SDS-molecular weight of 15 +/- 0.5 kD. The UV absorption spectra of Toxin CM36 showed a peak at 280 nm and an Emax at 343.8 nm, when excited at 280 nm fluorescence. Toxin CM36 had an LD50 of 3.5 microg/20 g (i.v.) in male albino mice. It exhibited neurotoxicity and produced irreversible blockade of isolated chick biventer cervicis and rat phrenic nerve diaphragm. The neurotoxicity was found to be Ca2+ dependent. Toxin CM36 had no significant effect on isolated guineapig heart and auricle. It also had no effect on blood pressure of cat and rat but produced respiratory apnoea in rat and guineapig. Toxin CM36 lacked phospholipase activity.

Animals↗

Antiinflammatory and antioxidant property of saponins of tea [Camellia sinensis (L) O. Kuntze] root extract.

Two groups of saponins, TS-1 and TS-2, isolated from tea root extract (TRE) were tested for antiinflammatory and in vitro antioxidant activity. Both TS-1 and TS-2 inhibited carrageenan-induced paw oedema in rats. The antioxidant activity of these compounds was evaluated using the xanthine-xanthine oxidase system. The study indicated that the previously observed antitumour activity of TRE might be mediated through scavenging of free radicals by saponins and their antiinflammatory activity.

Animals↗

Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent.

The antineoplastic effect of Trigonella foenum graecum seed extract has been evaluated in the Ehrlich ascites carcinoma (EAC) model in Balb-C mice. Intra-peritoneal administration of the alcohol extract of the seed both before and after inoculation of EAC cell in mice produced more than 70% inhibition of tumour cell growth with respect to the control. Treatment with the extract was found to enhance both the peritoneal exudate cell and macrophage cell counts. The extract also produced a significant antiinflammatory effect. We report here the antiinflammatory and antineoplastic effects, of Trigonella foenum graecum seed extract.

Animals↗

Multiple sclerosis: elevated expression of matrix metalloproteinases in blood monocytes.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) characterized by blood-brain barrier (BBB) breakdown. Disruptions of BBB continuity result in an influx of activated T cells and monocytes, and could contribute to lesion formation in the CNS. Matrix metalloproteinases (MMP) are enzymes implicated in BBB disruption, and in degradation of extracellular matrix proteins and myelin components. An imbalance in levels of MMP and tissue inhibitors of MMP (TIMP) has been implicated in the pathogenesis of MS. Since monocytes form a major cell population in acute MS lesions and may facilitate their entrance into the CNS by secretion of MMP, knowledge on MMP expression by blood monocytes could be useful to improve our understanding of the pathogenesis of MS. In the present study, we examined the expression of MMP-1, -3, -7, -9, -14 and TIMP-1 mRNA by blood monocytes in patients with MS using in situ hybridization. Levels of MMP-1, -3, -7, -9 and of TIMP-1 mRNA expressing monocytes were elevated in MS compared to controls, while those of MMP-14 did not differ. We therefore conclude that MS is associated with elevated levels of MMP and TIMP expressing blood monocytes that may contribute to MS pathogenesis.

Female↗

Adolescent maternal mortality in Mozambique.

PURPOSE: To describe adolescent maternal mortality and analyze its avoidability. METHODS: An audit approach was used to clarify the presence of avoidable factors in 239 maternal deaths, of which 22% were among adolescents. RESULTS: The main causes of adolescent death were malaria, pregnancy-induced hypertension, puerperal sepsis, and septic abortion. The audit classified as avoidable 75% of all maternal deaths. CONCLUSION: Adequate strategies addressing the special needs of adolescents are required to prevent currently high levels of maternal mortality in this age group.

Adolescent↗

Bleeding complications associated with the use of rt-PA versus r-PA for peripheral arterial and venous thromboembolic occlusions.

This article analyzes the early experience with alteplase (rt-PA) and reteplase (r-PA) to identify noteworthy differences in bleeding and to determine correlations with dosage, concomitant anticoagulation, and duration of infusion. A retrospective review of the medical records was unavailable for the initial 82 patients who were treated with either rt-PA (44) or r-PA (38) for peripheral arterial or venous occlusions after urokinase therapy. Successful recanalization was achieved in 31/44 (70%) of the patients treated with rt-PA and in 34/38 (89%) of the patients treated with r-PA. Significant bleeding was documented in 20/44 (45%) of the rt-PA-treated patients (including 14 transfusions) versus 3/38 (8%) of the r-PA-treated patients (3 transfusions). Concomitant anticoagulation with either preceding warfarin (international normalized ratio > 1.1) or a bolus of heparin at the outset of the infusion was associated with significant bleeding in 13/17 (76%) of the rt-PA-treated patients (including 9 transfusions) versus 0/17 in the r-PA-treated patients. No significant correlation between either mean dose or total dose and bleeding was shown for either drug. Early experience indicates that r-PA is at least as effective as rt-PA for the thrombolysis of peripheral arterial and venous occlusions. It also appears that r-PA is less likely than rt-PA to be associated with significant bleeding during such infusions, especially if the patient is concomitantly anticoagulated.

Adolescent↗

Serine proteinase inhibitors from eggs and larvae of tick Boophilus microplus: purification and biochemical characterization.

The present study describes the purification, characterization, and comparison of serine proteinase inhibitors during the development of egg and larva phases of the tick Boophilus microplus. Samples were collected of eggs between the first day of hatching and the beginning of eclosion (defined as El, E2, and E3) and of larvae between the first day of eclosion and the infectant phase (defined as L1, L2, and L3). Crude extracts of the samples (2.5% w/v in Tris-HCI buffer) were analyzed by SDS-PAGE, and showed three major protein bands of 42, 62, and 85 kDa, differing in intensity, from E1 to L3 samples. The total protein of the larva extracts was 34% less than that of the egg extracts, while no differences in active protein were detected. The apparent dissociation constant Ki determined for trypsin was 10-fold lower from E1 to L3 samples. Serine proteinase inhibitors from tick eggs and larvae (BmTls) were purified on trypsin-Sepharose column and analyzed by SDS-PAGE. The results showed a slight difference in protein pattern, with a protein band of 20 kDa in the E1 and E2 samples which did not appear in the other samples. The Ki for neutrophil elastase was 10-fold lower in L3 than E1. BmTI reverse-phase chromatography showed two and one major peaks in egg and larva samples, respectively. The N-terminal amino acid sequence of the L3 main peak from a C8 column showed a mix of BmTIs with the major sequence AVDFDKGCVPTADPGPCKG. Changes indicated by molecular weight and inhibition activity suggest different roles for BmTIs during the development process.

Amino Acid Sequence↗

A randomised, double-blind, placebo-controlled clinical trial of vitamin A in severe malaria in hospitalised Mozambican children.

This paper reports a randomised, double-blind, placebo-controlled clinical trial of the effect of routine vitamin A supplementation given on admission to children with severe malaria with regard to survival, recovery during hospitalisation and outcome 6 weeks after discharge. Children aged between 6 and 72 months admitted to the paediatric wards of the Central Hospital of Maputo (CHM), Mozambique with a diagnosis of severe malaria were randomly assigned either to a control group (placebo) or an experimental group (vitamin A) and were followed up 6 weeks after discharge. There were 280 children in the experimental and 290 in the placebo group. Seven (2.5%) and 13 (4.5%) children died in the experimental and the placebo groups, respectively, a relative risk of death of 0.56 (95% CI 0.23-1.38, p = 0.201). During the 1st 5 hours of admission, the relative risk of death in the vitamin A-supplemented group was 2.54 (0.50-12.96); after 5 hours of admission it was 0.19 (95% CI 0.04-0.85; p = 0.015). In the supplemented group, 4/82 (4.9%) of the children developed neurological sequelae vs 2/78 (2.6%) in the placebo group (RR = 1.90; 95% CI 0.36-10.09; p = 0.682). Although the overall reduction in the risk of death observed for all children receiving vitamin A is not statistically significant, it might be clinically important. This finding cannot, however, be accepted as a firm conclusion and requires validation by future trials.

Child↗

Haematinic effect of Hygrophila spinosa T. Anderson on experimental rodents.

Ethanolic extract of the aerial parts of H. spinosa a semiwoody herb was examined on male albino rats for certain haematological changes. The extract (100 & 200 mg/kg, po) significantly increased the haemoglobin, haematocrit, RBC and total WBC, as compared with vehicle treated control rat haemogram. In anemic male albino rats, the extract significantly increased haemoglobin, haematocrit and RBC count. Serum iron and serum total iron binding capacity were significantly decreased in H. spinosa extract treated anemic rats as compared with those in the vehicle treated anemic control rats. These findings demonstrated the haematinic effect of H. spinosa extract on experimental animals.

Animals↗

Boron compounds against human leukemic cells.

Two new boron compoumds, dihydroxy(oxybiguanido) boron (iii) hydrochloride monohydrate (HB) and guanidine biboric acid adduct (GB) were used in this study to observe the antitumor effect. Leukemic blast cells isolated from chronic myeloid leukemia (CML) patients showed significant cell growth inhibition within twentyfour hours. IC50 of GB and HB was 2mg/ml. The metabolically active cells were found to be inhibited by drug treatment as assessed by MTT test. Inhibition of 3H Thymidine incorporation also supported the above result. In this study we investigated the molecular mechanisms by which HB and GB induce apoptosis in immature blast cells.

Apoptosis↗

Isolation, purification and partial chemical characterization of a lethal factor from common indian toad (Bufo melanostictus, Schneider) skin extract.

Indian toad (Bufo melanostictus, Schneider) skin extract (TSE) is pharmacologically potent and probably contains several bioactive compounds [Das et. al., Indian J Pharmacol, 28 (1996) 72]. A lethal factor was isolated and purified by neutral alumina column chromatography followed by HPLC. Spectroscopic (UV, IR, FAB-MASS) study indicated that the lethal factor (TSE-LF) was a 254 Da long chain compound with carbonyl, hydroxyl and ester as functional groups. LD50 of TSE-LF was found to be 3.5 mg/kg (iv). Biological study showed that TSE-LF possesses hypotensive, cardiotoxic, neurotoxic activity and produced death by apnoea in experimental animal. Cyproheptadine antagonised TSE-LF induced contraction of isolated smooth muscle indicating involvement of histamine/serotonin receptors. TSE-LF induced neurotoxic action on chick biventer cervices was mediated through Ca2+ ion.

Animals↗

A sleep inducing factor from common Indian toad (Bufo melanostictus, Schneider) skin extract.

Bufo melanostictus (common Indian toad) acquire different bioactive substances in their skin during their life-time in wide ecological habitat. Earlier investigation from this laboratory revealed that toad (B. melanostictus) skin extract (TSE) posses different bioactive compounds of different diversity (Das, M., Auddy, B. and Gomes, A., 1996. Pharmacological study of the toad skin extract on experimental animals. Indian J. Pharmacol. 28, 72-76). Among these sleep induction and sleep potentiation indicated the possibility of sleep inducing factor(s) in TSE. One such sleep inducing factor (SIF) was isolated and purified by neutral alumina column chromatography followed by HPLC. Spectroscopy (UV, IR, FAB-MASS) study indicated that the sleep inducing factor was a 880 Dalton conjugated aromatic compound with a hydroxyl and carbonyl functional group. Biological study showed that SIF produced no lethality in male albino mice upto the dose of 8 mg/kg, i.v. Cyproheptadine antagonised SIF induced contraction of isolated smooth muscle indicating histamine/serotonin receptor mediated action of SIF. EEG studies showed that SIF increased sleep and decreased awakening condition of freely moving rats. Biochemical studies showed that SIF produced significant alteration of brain biogenic amine levels, monoamine oxidase (MAO) and tryptophan hydroxylase (TH) activity. This may be the reason of SIF induced sleep, although the SIF induced sleep mechanism needs further detail investigation.

Animals↗

Haemorrhagic protein of Russell's viper venom with fibrinolytic and esterolytic activities.

A haemorrhagic toxin specifically active on skin and muscle at the site of introduction in mice has been purified from Vipera russelli russelli (Indian subspecies of Russell's viper) venom by CM-Sephadex C-50 ion exchange chromatography and size exclusion (SE)-HPLC. This toxic protein also has strong fibrinolytic and arginine esterolytic activities. The purified preparation was a single polypeptide chain of molecular weight 73,000, as revealed by SDS-PAGE and SE-HPLC under native and denatured conditions. It has been named as VRR-73. Atomic absorption spectrometry indicated the existence of Mg(2+) in a mol per mol ratio. Antiserum was effective in neutralizing haemorrhage when administered immediately following VRR-73 but was ineffective in inhibiting fibrinolytic and esterolytic activities. On the other hand phenylmethyl sulphonyl fluoride and EDTA inhibited fibrinolysis and esterolysis but did not affect haemorrhage. Thermal denaturation of VRR-73, after exposure at 100 degrees C for 10 min, led to inactivation of all of its activities. Fibrinolytic and esterolytic activities, but not the haemorrhagic activity, were slowly regained after cooling at 25 degrees C. Thus the two pathological activities of VRR-73 appear to be associated with two different regions of the molecule.

Animals↗