Methanolic extract of Hemidesmus indicus root augments the antibacterial and antibiofilm activity of amoxicillin and clindamycin against methicillin-resistant Staphylococcus aureus of bovine origin.

The present study evaluated the antibacterial and antibiofilm activity of methanolic extract of Hemidesmus indicus root (MHIR) in combination with amoxicillin and clindamycin against biofilm-forming methicillin-resistant Staphylococcus aureus (MRSA) isolated from milk samples of mastitic cows. Microdilution susceptibility testing and microtitre plate assays were used to evaluate the in vitro efficacy of MHIR and antibiotic combinations against MRSA (n = 12). Furthermore, in vitro findings were validated in a murine model. Minimum inhibitory concentration and minimum biofilm inhibitory concentration of amoxicillin and clindamycin in combination with MHIR were significantly (P < 0·05) lower than when used alone against MRSA. In terms of antibacterial activity, MHIR showed additive interaction (fractional inhibitory concentrationindex >0·5-4) with amoxicillin and clindamycin against all the MRSA isolates, whereas MHIR synergizes (fractional biofilm inhibitory concentrationindex ≤0·5) the antibiofilm activity of amoxicillin and clindamycin against 58·33% and 83·33% of the MRSA isolates respectively. Amoxicillin/clindamycin in combination with MHIR significantly (P < 0·05) reduced disease activity score, and bacterial load and Gram-positive spots in kidney and liver of MRSA-infected mice. The combined efficacy of MHIR and amoxicillin/clindamycin was comparable to clindamycin alone but superior to amoxicillin alone. Hence, the combination of MHIR with amoxicillin/clindamycin is advocated in the treatment of MRSA-associated infections.

Versatility Of Square Flaps In Post-Burn Contractures Involving Upper Limb.

Post-burn contractures are a common problem and functionally limiting for upper limbs. Many different techniques have been described in the literature for their treatment. Z-plasty and release with SSG cover are the commonest procedures done for post-burn contractures. In this study we assess the use of the square flap technique in post-burn contractures of upper limb. Eleven patients with a total number of twelve upper limb contractures (mild to moderate) involving axilla, elbow and finger underwent release by standard square flap technique. All cases were followed up for at least 6 months and analyzed for range of motion and aesthetic outcome. Patient and surgeon satisfaction was recorded. All operated cases achieved a satisfactory range of movement post-operatively without any recurrence. The number of patients who were satisfied with the surgery were 7 out of 11, and 4 patients were somewhat satisfied with the results obtained. In contrast, the surgeons were satisfied in all cases. Square flap is shown to be an easy and reliable flap for mild to moderate contractures of the anterior or posterior axillary folds, elbow contractures and finger contractures with low recurrence rate.

Les rétractions séquellaires de brûlure sont fréquentes et engendrent des limitations fonctionnelles au membre supérieur. Beaucoup de techniques différentes ont été décrites dans la littérature pour leur traitement : plastie en Z, libération et couverture par greffe de peau, sont les techniques les plus couramment utilisées. Dans cette étude, nous évaluons l'usage du double lambeau rhomboïde ou lambeau carré de Hyakusoku dans les rétractions séquellaires de brûlure du membre supérieur. 11 patients représentant 12 rétractions au membre supérieur (minimes à modérées) intéressant la région axillaire, le coude, et les doigts ont bénéficié d'une libération de la rétraction par la technique du double lambeau rhomboïde ou lambeau carré de Hyakusoku. Tous les patients ont été suivis pendant au moins six mois post-opératoire. L'analyse porte à la fois sur les mobilités et le résultat esthétique. La satisfaction du patient et du chirurgien a été notée. Toutes les interventions ont permis une nette amélioration de la fonction, sans récidive. 7 patients sur 11 ont été satisfaits par le résultat du geste chirurgical et quatre patients ont été assez satisfaits. En revanche, les chirurgiens ont noté les résultats comme satisfaisants dans tous les cas. Le double lambeau rhomboïde ou lambeau carré de Hyakusoku semble donc être un lambeau simple et fiable dans le traitement des rétractions minimes à modérées des piliers axillaires antérieur ou postérieur, du coude ou des doigts avec un très faible taux de récidive.

School-age Children as Asymptomatic Malaria Reservoir in Tribal Villages of Bastar Region, Chhattisgarh.

Malaria is a major health concern in India, especially in regions populated by tribals. In this cross-sectional survey carried out in Bastar region of Chhattisgarh, 35 Plasmodium infections were detected in 451 participants screened during the non-transmission season; 27 (77.1%) were asymptomatic. Participants with age 6-14 years were at high risk of asymptomatic infection [OR 4.09, 95% CI, 1.69 to 9.89, P=0.001], and may act as an under-appreciated reservoir for sustained malaria transmission.

Monitoring of long-lasting insecticidal nets (LLINs) coverage versus utilization: a community-based survey in malaria endemic villages of Central India.

BACKGROUND: Despite the known effectiveness of long-lasting insecticidal nets (LLINs) in providing protection against malaria, high level of ownership and use are very difficult to achieve and maintain. Nearly 40,000 LLINs were distributed in 2014 as an intervention tool against malaria transmission in 80 villages of Keshkal sub-district in Chhattisgarh, India. This study assessed LLIN coverage, access, utilization pattern, and key determinants for the net use 1 year after mass distribution. METHODS: In 2015, a cross-sectional household survey was carried out in 80 study clusters (whole village or part of village). From each cluster, 40 households were randomly selected and interviewed using a structured questionnaire adapted from the malaria indicator survey of Roll Back Malaria guidelines. Information on demographic characteristics, LLIN ownership, and its use on the night before the survey, and physical condition of LLINs were recorded. RESULTS: 2970 households were interviewed with a total of 15,003 individuals present in the households during the night before the survey. Nearly 98% of households had at least one LLIN and 59.4% of the surveyed population reportedly used an LLIN the previous night. LLIN use varied from 41 to 94% between the study clusters. Nearly 89% of the LLINs were found in good physical condition (without holes). However, proportion of household with at least one LLIN per two persons was only 39%. CONCLUSION: Universal coverage of LLINs was inadequate in the study clusters making it difficult for all household members to use an LLIN. LLIN use varied between clusters and was highest in children under 5 years of age. Health education campaigns and creating awareness about the benefit of sleeping under the LLINs in providing protection against malaria is required not only to high risk groups of pregnant women and children below 5 years of age but all the members of the family to have an epidemiological impact of this intervention at the community level. Relatively high net use despite poor access to LLINs indicates an overall desire to use nets when they are available. The main barrier to increased use of nets is the low coverage at household level.

Involvement of Mitanins (female health volunteers) in active malaria surveillance, determinants and challenges in tribal populated malaria endemic villages of Chhattisgarh, India.

BACKGROUND: Accredited Social Health Activists (ASHA), female health volunteers working at village level have become an integral component of National Health Mission (NHM) in India in the past two decades. Mitanin (meaning female friend in local dialect), a precursor of ASHA, play an indispensable role in early detection of health related problems and are helping in improving overall community health status in Chhattisgarh state. The current study was carried out to evaluate the feasibility of involving Mitanin in active malaria surveillance work in 80 tribal villages of Chhattisgarh and to explore the challenges and determinants to perform malaria surveillance activities by the Mitanins. METHODS: A total of 162 Mitanins were selected and divided into two age and village matched groups. The first group (training plus) of Mitanins were given additional training in malaria surveillance activities in whilst the second (standard) group received routine training. All Mitanins were interviewed using a structured questionnaire. In-depth interviews were also conducted among randomly selected sub groups of Mitanins (five from each group) after the completion of the quantitative survey. Performance of Mitanins was evaluated using pre-defined grading scores (A-E) which included various factors such as educational qualifications and knowledge about malaria, its signs and symptoms and knowledge, attitude and treatment practices. RESULTS: More number of Mitanins in training plus group has showed better performance (≥ B) than those in the standard group of Mitanins (80% vs 43.5%, p = 0.001) after adjusting for socio-demographic factors. Based on the outcome of in-depth interviews, Mitanin's lack of adequate support from supervisors, delayed payment of incentives and lack of appreciation were the major challenges mentioned. CONCLUSION: Mitanins can play an effective role in active fever surveillance for malaria besides performing other health related tasks at sub-village level after focused education on malaria related activities and proper supervision.

Fluoride enrichment in an alluvial aquifer with its subsequent effect on human health in Birbhum district, West Bengal, India.

This research work primarily deals with the geochemistry and genesis of fluoride (F-) in an alluvial aquifer with an emphasis on prevalence of dental and skeletal fluorosis among the endemic population. Hydrogeochemical outcomes reveal that chemical weathering and ion-exchange phenomena are the two dominant processes that make study area groundwater into NaHCO3 water type. Presence of intercalated zeolite rich sediments (FTotal 412-446 mg/kg) having higher ion-exchange capacity (120-125 meq/100 g) within the aquifer is the source and mobilizing factors of F- in groundwater respectively. Laboratory experiment further justifies higher desorption potential of aquifer sediments at the groundwater pH of 6.5-7.5. Health survey reveals that out of 235 studied population 60% suffer from dental fluorosis while females >30 years of age became exposed early to osteoporosis disease.

Inferring the fluoride hydrogeochemistry and effect of consuming fluoride-contaminated drinking water on human health in some endemic areas of Birbhum district, West Bengal.

This research work is carried out to evaluate fluoride (F) hydrogeochemistry and its effect on the population of two endemic villages of Birbhum district, West Bengal. Fluoride concentration in drinking water varies from 0.33 to 18.08 mg/L. Hydrogeochemical evolution suggests that ion-exchange mechanism is the major controlling factor for releasing F in the groundwater. Most of the groundwater samples are undersaturated with respect to calcite and fluorite. Health survey shows that out of 235 people, 142 people suffer from dental fluorosis. According to fluoride impact severity, almost 80 and 94 % people in an age group of 11-20 and 41-50 suffer from dental and skeletal fluorosis, respectively. Statistically drinking water F has a positive correlation with dental and skeletal fluorosis. Bone mineral density test reveals that 33 and 45 % of the studied population suffer from osteopenic and osteoporosis disease. IQ test also signifies that F has a bearing on the intelligence development of the study area school children. The existence of significant linear relationship (R (2) = 0.77) between drinking water F and urinary F suggests that consumption of F-contaminated drinking water has a major control over urinary F (0.39-20.1 mg/L) excretion.

Free thin anterolateral thigh flap for post-burn neck contractures - a functional and aesthetic solution.

Neck contractures after burn injuries produce restrictions in motion and unacceptable aesthetic outcomes. Although different methods of reconstruction have been used in the treatment of this ailment, a limited and unsatisfactory outcome often results. Free thin anterolateral flaps have been found to be a good single stage option for reconstruction of post-burn contractures of the neck. In our study, 11 patients with post flame burn contractures of the neck underwent surgical release and coverage by a free thin anterolateral thigh flap. Patients were followed up for an average of five years and various aspects of functional and aesthetic rehabilitation were assessed. Our findings revealed that the free thin anterolateral flaps covered the defects over anterior and lateral aspects of the neck with good colour match and contour. Furthermore, none of the flaps had any significant early or delayed complications. Two cases had to be reoperated for partial loss of flaps and all patients were satisfied with functional and aesthetic outcomes. We therefore consider free thin anterolateral thigh flaps to provide a good single stage reconstruction for post-burn cervical contractures with good functional and aesthetic outcomes.

Les contractures du cou en suite des brûlures produisent des restrictions en mouvement et les résultats esthétiques inacceptables. Bien qu'il y ait différentes méthodes de reconstruction dans le traitement de cette affection, il y a souvent un résultat limité et insatisfaisant. Les lambeaux libres antérolatérales minces ont été trouvés à être une bonne option en une seule étape pour la reconstruction des contractures du cou post-brûlures. Dans notre étude, 11 patients atteints de contractures du cou en suite d'une brûlure causée par la flamme ont subi la libération chirurgicale et la couverture par un lambeau libre antérolatérale mince de la cuisse. Les patients ont été suivis pendant une moyenne de cinq ans et de divers aspects de la réadaptation fonctionnelle et esthétique ont été évalués. Nos résultats ont révélé que cette solution a refait la surface des défauts plus antérieure et latérale du cou avec une bonne correspondance des couleurs et des contours. En outre, aucun des lambeaux avait des complications précoces ou tardives importantes. Deux cas ont dû être réopérés pour une perte partielle de lambeaux. Tous les patients étaient satisfaits des résultats fonctionnels et esthétiques. Enfin, nous considérons cette solution adéquate pour assurer une bonne reconstruction en une seule étape pour les contractures cervicales post-brûlures avec de bons résultats fonctionnels et esthétiques.

Synchronous renal malignancy presenting as recurrent urinary tract infections.

Renal cell carcinoma (RCC) and urothelial carcinoma of the upper urinary tract are not uncommon urological malignancies. Their simultaneous occurrence in a patient is, however, extraordinarily rare. We report the case of a patient who underwent unilateral nephrectomy for suspected RCC and diagnosed transitional cell carcinoma of the superior pelvis. Preoperative imaging was suspicious for renal pelvic involvement, which was confirmed upon performing cystoscopy and biopsy of the suspected lesion preoperatively. This preoperative approach was especially appropriate as a nephron saving procedure was being considered prior to the discovery of the synchronous lesion. We discuss this rare simultaneous occurrence of synchronous malignancies in the same kidney.

The studies on nutrient balances in crossbred cattle bulls fed chopped green sugarcane tops supplemented with some agro industrial by- products.

Fifteen adult crossbred cattle bulls, 18-22 months old (mean body weight 286.33 + 9.43) were divided into 3 groups following RBD design and were fed sugarcane tops (SCT) supplemented with some agro-industrial byproducts and concentrate feeds to determine nitrogen, Ca and P in crossbred cattle bull. For this purpose, crossbred cattle bulls were fed for 30 days ad lib SCT supplemented with Wheat bran (WB), Lentil chuni (LC) and WB + LC (50:50) in Group I, II, and III respectively. The balance values were 15.28 + 2.70, 26.85 + 4.35 and 18.00 + 3.17 for nitrogen, 11.77 + 1.34, 12.94 + 2.96 and 15.38 + 1.15 for calcium, 11.74 + 0.64, 11.26 + 1.58 and 11.69 + 0.79 for phosphorus in group I, II and III, respectively. There were no significant differences among the experimental groups in Ca and P balance values but balance of nitrogen was significantly (P < 0.05) higher in group II as compared to group I and III. It may indicated that the rumen fermentation was more appropriate in group III where animals were fed 50% lentil chuni and 50% wheat bran (supplementation of both protein and energy).

Blood schizontocidal activity of selected 1,2,4-trioxanes (Fenozans) against the multidrug-resistant strain of Plasmodium yoelii nigeriensis (MDR) in vivo.

Blood schizontocidal activity of 10 selected cis-fused cyclopenteno-1,2,4-trioxanes (namely Fenozan compound nos 6, 7, 11, 27, 32, 39, 44, 45, 48 and 51) have been re-investigated to establish their curative doses against the multidrug-resistant Plasmodium yoelii nigeriensis strain, which is lethal in Swiss mice. Freshly prepared formulations of these compounds prepared either in neutral groundnut (peanut) oil or in dimethyl sulfoxide (DMSO)-Tween-water, were compared for their antimalarial activity. Only 2 compounds, namely Fenozan derivatives 11 and 45, formulated in neutral groundnut oil for oral administration, showed highest activity with 100% cure rate in MDR P. yoelii nigeriensis-infected mice, while the DMSO-Tween-water formulations were inactive. Fenozan-48 produced 72.2% cure, when administered orally in groundnut oil (formulation) while its DMSO-Tween formulation was inactive. In the case of Fenozan 7, the oil and DMSO-Tween formulations produced 92.3 and 76.0% cures respectively. Fenozan derivatives nos 6, 27, 32, 39, 44 and 51 were not protective either in groundnut oil or DMSO-Tween oral formulations. The present study has applied more rigorous criteria for selection of active compounds, and has identified the 3,3-spirocyclopentane derivative Fenozan 11, and the 3,3-spirohydropyran derivative Fenozan 45, as potential blood schizontocides which can completely eliminate multidrug-resistant malaria infection in mice. Both these compounds are candidates for pre-clinical development. The present study advocates the preferred use of an oil vehicle for oral evaluation of potential antimalarial trioxanes/fenozans instead of the DMSO formulation, which gives inferior curative efficacy.

Blood schizontocidal activity of azithromycin and its combination with alpha/beta arteether against multi-drug resistant Plasmodium yoelii nigeriensis, a novel MDR parasite model for antimalarial screening.

Many different drug-resistant lines of rodent malaria are available as screening models. It is obligatory to screen new compounds for antimalarial activity against a series of resistant lines in order to identify a compound with potential for the treatment of multi-drug resistant (MDR) malaria infections. Instead of using a battery of resistant lines, a single MDR Plasmodium yoelii nigeriensis strain that shows a wide spectrum of drug resistance to high doses of chloroquine, mepacrine, amodiaquine, mefloquine, quinine, quinidine, halofantrine as well as tetracyclines, fluoroquinolines and erythromycin, was used to assess the blood schizontocidal efficacy of a new macrolide azithromycin and other antibiotics. The present study shows that only azithromycin has the potential to control an MDR P. y. nigeriensis infection in Swiss mice, provided the treatment with a dose of 50-100 mg/kg/day by oral route is continued for a period of 7 days. Tetracycline, oxytetracycline, doxycyline, erythromycin, ciprofloxacin and norfloxacin, although active in vitro, failed to protect the mice. Tetracycline, ciprofloxacin and norfloxacin combinations with chloroquine did not control the infection. Additionally, the antimalarial efficacy of azithromycin can be potentiated with the addition of arteether, which is an ethyl ether derivative of artemisinin. A total (100%) curative effect has been obtained with a shorter regimen of 4 days only.

Plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound CDRI 80/53 (elubaquine) in rhesus monkeys.

The gametocytocidal action of a new enamine analogue of primaquine, elubaquine (compound CDRI 80/53, bulaquine), has been evaluated against Plasmodium cynomolgi B in rhesus monkeys. Colony bred Anopheles stephensi mosquitoes were fed on gametocyte carrying rhesus monkeys prior to and at varying intervals after oral administration of a single dose of elubaquine at doses ranging between 0.63 and 5.00 mg/kg. Complete loss of oocyst development and mosquito infectivity was observed within 24 h after administering a single 1.25 mg/kg dose, while higher dose of 3.75 mg/kg inhibited oocyst development within 5 h, indicating gametocytocidal action of the compound. Elubaquine did not show any action against developing oocysts in the vector.

Mefloquine resistance reversal action of ketoconazole - a cytochrome P450 inhibitor, against mefloquine-resistant malaria.

Plasmodium knowlesi (W1) shows a high level of innate resistance to mefloquine as shown by recrudescence of blood-induced infection in rhesus monkeys, following oral mefloquine treatment with up to 80-160 mg/kg total dose over 3-4 days. Ketoconazole, at a dose of 75 mg/kg/day x 10 days given orally to P. knowlesi-infected rhesus monkeys, exerted a suppressive antimalarial effect in 1 of the 2 monkeys as evidenced by a delayed recrudescence (on day 30) and curative action in case of the other monkey, whereas a lower dose of ketoconazole (25 mg/kg/day x 10 days) failed to suppress infection effectively. When ketoconazole at a low dose (25 mg/kg/day x 10 days) treatment was combined with mefloquine (20 mg/kg/ day x 4), 1 of the 2 infected monkeys was cured, while the combination of a higher dose of ketoconazole (75 mg/kg/day x 10 days) with mefloquine (20 mg/kg/day x 4), had a complete curative effect on P. knowlesi infection in all the treated monkeys (7/7). Besides exerting direct antimalarial action against a mefloquine-resistant P. knowlesi, ketoconazole also acts as an inhibitor of hepatic microsomal CYP4503A, which regulates and slows down mefloquine biotransformation to carboxymefloquine, resulting in a possible elevation of the effective plasma drug level, which seems to be responsible for elimination of the resistant P. knowlesi. The study shows a resistance reversal effect of a ketoconazole - mefloquine combination that could be exploited for the control of mefloquine-resistant malaria infection. The study shows that ketoconazole can reverse mefloquine resistance of P. knowlesi. These findings can also be applied to reverse mefloquine resistance of P.falciparum in areas where mefloquine resistance is already established. The precise role of parasite CYP450 in mefloquine resistance and its possible role, if any, in expelling the intracellular mefloquine from the resistant plasmodia still remains to be elucidated.

Resistance reversal action of ketoconazole against mefloquine resistance of Plasmodium yoelii nigeriensis.

Ketoconazole at 200 mg/kg dose has been found to exert marginal antimalarial action against multidrug resistant (MDR) Plasmodium yoelii nigeriensis (P. yoelii nigeriensis) in Swiss mice with 25% protection (2/8 mice) while at lower Ketoconazole dose i.e., 75-100 mg/kg, 14.28% mice were protected. Mefloquine (MFQ) (at 8 and 16 mg/kg) exerted suppressive action against MDR P. yoelii nigeriensis resulting in 25 and 14.28% protection of mice respectively. Combined treatment with Ketoconazole and mefloquine resulted in protection of 5/6 mice (83.33%) at MFQ 4 mg/kg + Ketoconazole 100 mg/kg dose, 7/8 (87.5%) mice at MFQ 8 mg/kg + Ketoconazole 20 mg/kg dose and 5/7 (71.42%) mice at MFQ 16 mg/kg + Ketoconazole 25 mg/kg dose and 5/6 (83.33%) mice at MFQ 16 mg/kg + Ketoconazole 100 mg/kg dose. Ketoconazole has been found to enhance the protective effect of mefloquine against MFQ resistant P. yoelii nigeriensis resulting in 66-88% protection of the mice treated with the appropriate combinations. The combination also increased suppression of parasitaemia at different times. The Ketoconazole combination with MFQ significantly increased the mean survival time of the treated mice compared to individual drugs alone. The study shows that Ketoconazole when administered with MFQ exerts bio-enhancing action against mefloquine resistance of MDR P. yoelii nigeriensis.

Blood schizontocidal activity of WR 238605 (Tafenoquine) against Plasmodium cynomolgi and Plasmodium fragile infections in rhesus monkeys.

A new 8-aminoquinoline antimalarial WR 238605 (Tafenoquine), developed initially as a primaquine alternative for prevention of Plasmodium vivax relapses was evaluated for blood schizontocidal activity against two simian malaria infections namely Plasmodium cynomolgi B and Plasmodium fragile in rhesus monkeys. Treatment with WR 238605 at a dose of 3.16 mg(base)/kg/day x 7 days cured established trophozoite induced infections in monkeys with both these parasites. The lower dose of 1.00 mg/kg/day cured 9 out of 12 monkeys infected with P. cynomolgi B and 10 out of 11 monkeys infected with P. fragile. Primaquine was only partially curative at 10.0 mg(base)/kg/day x 7 dose regimen against both these infections. The potent blood schizontocidal activity of tafenoquine adds to the armoury of antimalarial drugs.

Antagonist effect of chloroquine and tumor necrosis factor on hepatic oxidative stress and antioxidant defense in normal and Plasmodium yoelii nigeriensis-infected mice.

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Tumor necrosis factor (TNF) has been implicated in the pathogenesis of malaria by production of reactive oxygen species. Chloroquine is a traditionally used antimalarial and has been postulated to inhibit TNF secretion during malaria infection. OBJECTIVE: The study the comparative effect of chloroquine and TNF treatment on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis-infected mice. MATERIALS AND METHODS: The mice were divided into six groups, each consisting of four to six animals. They were normal mice, normal mice treated with chloroquine, normal mice treated with TNF-alpha, P. y. nigeriensis-infected mice, P. y. nigeriensis-infected mice treated with chloroquine and P. y. nigeriensis-infected mice treated with TNF-alpha. RESULTS: Chloroquine treatment of the normal mice caused no significant alterations in hepatic oxidative stress and antioxidant defense indices while TNF treatment of normal mice caused a significant decrease in hepatic superoxide dismutase. Chloroquine treatment of P. y. nigeriensis-infected mice caused a decrease in blood parasitemia which was accompanied by restoration of altered indices to near normal levels. However, TNF treatment of P. y. nigeriensis-infected mice had no effect on blood parasitemia but caused a significant increase of hepatic xanthine oxidase and lipid peroxidation and a decrease in the activity of hepatic superoxide dismutase. CONCLUSION: Exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of the antioxidant defense enzyme SOD, while chloroquine treatment reduces the severity of malaria infection by decreasing the blood parasitemia and also perhaps by inhibiting the TNF release.

Inactivation of chloramphenicol by Staphylococcus aureus biotype C from humans & animals.

During an investigation, 55 biotype C (bovine and caprine biotype) Staphylococcus aureus isolated from 43 cows suffering from mastitis, and 20 biotype C Staph. aureus strains from the nares and the side of nail-tips of the right thumbs of 20 farm workers (milkers and animal attendants) on six small dairy farms in Assam and Meghalaya were isolated. Three strains from the former and six strains from the latter from among the isolates on two of the farms were found resistant to chloramphenicol, when tested with a routine susceptibility test. Test of the organisms by the agar dilution method indicated that the resistant strains had a minimal inhibitory concentration for chloramphenicol of 32 micrograms/ml or more, while, the chloramphenicol sensitive strains and two reference strains, Staph. aureus ATCC 25923 and Micrococcus luteus ATCC 9341, had < or = 8 micrograms/ml. Two bovine and five human chloramphenicol resistant strains showed positive results when tested by the Gots test. When these strains were tested by a standard method in broth, containing 30 micrograms chloramphenicol per ml, all showed evidence of inactivating chloramphenicol up to a non-detectable level within 36 h. Inactivation of chloramphenicol by Staph. aureus has clinical significance.

Pyronaridine: an effective antimalarial against multidrug-resistant malaria.

Pyronaridine, administered intramuscularly (im) to Swiss mice infected with the lethal multidrug-resistant Plasmodium yoelii nigeriensis, was found to exert high blood schizontocidal activity. The efficacy of doses of pyronaridine ranging from 0.625 to 30 mg (base/kg) was evaluated using a 4 day treatment schedule (drug was administered at 0, 24, 48 and 72 hrs). It was found that doses of 2.5mg/ kg and higher protected animals completely from the lethal effects of the parasite. The same degree of protection was found when the treatment duration was reduced to 3 days. This study shows that pyronaridine is a potentially useful antimalarial drug that could be exploited for the control of multidrug-resistant malaria infection.

Plasmodium yoelii nigeriensis (MDR)-efficacy of oral pyronaridine against multidrug-resistant malaria in Swiss mice.

A multidrug-resistant strain of Plasmodium yoelii nigeriensis (MDR) showing a wide spectrum of resistance to chloroquine, amodiaquine, mepacrine, mefloquine, halofantrine, quinine, and quinidine was used in this study for in vivo evaluation of the blood schizontocidal activity of pyronaridine, a topoisomerase II inhibitor, in Swiss mice. The parasite produces 100% lethal infection in mice. The drug was administered orally once a day from day 0 onward. The initial studies showed that low doses of pyronaridine (0.625 to 5.0 mg base/kg x9 days) did not completely control blood-induced P. yoelii nigeriensis infection. Finally a series of doses of pyronaridine ranging from 1.25 to 30.0 mg/kg administered orally for 7 consecutive days were evaluated and in spite of high level of resistance to standard antimalarials, the parasite P. yoelii nigeriensis has shown complete susceptibility to pyronaridine (15 mg/kg dose x7 days). The present paper also compares the merits of a single MDR strain vs a battery of different resistant lines for quick antimalarials screening.