Drug targets for resistant malaria: Historic to future perspectives.

New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria.

Therapeutic journery of nitrogen mustard as alkylating anticancer agents: Historic to future perspectives.

Cancer is considered as one of the most serious health problems today. The discovery of nitrogen mustard as an alkylating agent in 1942, opened a new era in the cancer chemotherapy. This valuable class of alkylating agent exerts its biological activity by binding to DNA, cross linking two strands, preventing DNA replication and ultimate cell death. At the molecular level, nitrogen lone pairs of nitrogen mustard generate a strained intermediate "aziridinium ion" which is very reactive towards DNA of tumor cell as well as normal cell resulting in various adverse side effects alogwith therapeutic implications. Over the last 75 years, due to its high reactivity and peripheral cytotoxicity, numerous modifications have been made in the area of nitrogen mustard to improve its efficacy as well as enhancing drug delivery specifically to tumor cells. This review mainly discusses the medicinal chemistry aspects in the development of various classes of nitrogen mustards (mechlorethamine, chlorambucil, melphalan, cyclophosphamide and steroidal based nitrogen mustards). The literature collection includes the historical and the latest developments in these areas. This comprehensive review also attempted to showcase the recent progress in the targeted delivery of nitrogen mustards that includes DNA directed nitrogen mustards, antibody directed enzyme prodrug therapy (ADEPT), gene directed enzyme prodrug therapy (GDEPT), nitrogen mustard activated by glutathione transferase, peptide based nitrogen mustards and CNS targeted nitrogen mustards.

Situs inversus with dextrocardia with multiple cardiac lesions in adult.

Situs inversus with dextrocardia is the malposition most likely to occur with structurally normal heart; generally discovered on routine chest x-ray or physical examination performed for other reasons. These persons experience normal longevity of life and have similar risk of getting acquired disease as that of other person of same age and sex group. Symptoms related to acquired disorder may also lead to discovery of such cardiac malposition. Incidence of congenital cardiac anomalies in dextrocardia with situs inversus is very low globally but its figure in Nepal is not known. We report an adult of 43 years age having situs inversus with dextrocardia associated with multiple cardiac lesions i.e. ventricular septal defect, aortic regurgitation, mitral regurgitation and tricuspid regurgitation.

Application of in vitro methods for selection of Lactobacillus casei strains as potential probiotics.

Probiotics have established their efficacy as dietary adjuncts providing benefits to consumers, but the selection of probiotics before incorporation in diet requires close scrutiny in the form of in vitro as well as in vivo tests. The present study was undertaken to check different in vitro characteristics of seven Lactobacillus casei strains. The characteristics studied include acid and bile tolerance, adhesion and cell surface hydrophobicity, antimicrobial effect on common pathogens and cholesterol reduction. All strains were able to resist pH 3 for 3 h, though resistance to pH 2 was exhibited by NCDC 17, C1 and Y strains only. NCDC 63 and VT strains were able to tolerate 1% and 2% bile concentrations for 12 h. There was wide variation in ability of strains to adhere to isolated rat epithelial cells. The index was highest for C1 at 66%. The electron microscopic adhesion studies on the stainless steel chips did not reveal any specific attachment to surfaces by any of strains. The hydrophobic character for octane was highest for strain C1 at 54.06% and lowest for strain C2 at 4.65%. The ability to antagonize common pathogens was observed in all strains but this activity was attributed to production of organic acids and no specific compound caused the inhibitory effect. The cholesterol reducing ability varied not only for strains but also for time of incubation. NCDC 17 showed maximum reduction in cholesterol level after 48 h of incubation with buffalo plasma as the source of cholesterol. Overall there existed variations in different strains with respect to different characters of significance to be a probiotic.

COMPARISION OF DIURETIC ACTIVITY OF ETHANOLIC EXTRACT OF AERVA LANATA (Linn.) Juss. ex. Schult & AERVA TOMENTOSA Forsk. Family: AMARANTHACEAE.

The diuretic activity of concentrated ethanolic extract of Aerva lanata (Linn) & Aerva tomentosa Forsk on healthy albino rats were studied with frusemide as reference drug. The urine output increased with concentrated ethanolic extract of Aerva lanata only. In this case the level of electrolytes in urine also increased. But the diuretic activity was mild as compared to frusemide.

Antispasmodic activity of the crude and purified oil of mesua ferrea seed.

The crude native oil and purified seed oil of Mesua ferrea were studied for their effect on isolated rat il eum by taking standard spasmodic and antispasmodic drugs. The crude oil of seed showed significant antispasmodic activity but purified oil was devoid of any antispasmodic activity.

Rapid identification of viable bacterial spores using a fluorescence method.

A method has been devised to differentiate viable and nonviable bacterial spores. "Germination-like" changes are initiated in spores with performic acid and lysozyme. The germinated spores are stained with aqueous acridine orange, a fluorescent dye. Nonviable spores fluoresce lemon-green and viable spores orange-red. It is proposed that with the use of a membrane filter resistant to performic acid and lysozyme, the method may be used for spore enumeration in foods in about 4 hr compared to conventional plating methods, which usually require up to 72 hr.

A study on some diarrhoea related practices in urban Mirzapur.

In an operational research on the improvement of sanitation and water supply by an Indo-Dutch project at Mirzapur, UP, diarrhoeal morbidity was taken as an intermediate outcome variable for measuring the impact of the proposed intervention. In this study 350-410 under-five children were selected from 200 urban families of 3 slums and surveyed during 3 different seasons for 2 weekly recall of morbidity, treatment and feeding practices during diarrhoea. The prevalence of diarrhoea varied between 8.7% to 33%. Breast feeding was not restricted while other forms of feeding was continued in 57.1% to 66.3% of cases. Use of ORT increased significantly from 0% to 39.62% possibly as a result of health education. Reorientation of private practitioners to avoid use of unnecessary drug is suggested.

PIP: In 1988, researchers conducted an operations research study of an improved sanitation and water supply project which included health education in the slums of Sabari, Armanganj, and Katwaru Ka Pura in Mirzapur, Uttar Pradesh in India to examine diarrhea related practices. Diarrhea prevalence was significantly higher in the rainy season than either the summer or winter months (32.3% vs. 12.9% and 8.65% respectively; p.001). Drugs were used significantly more often in the rainy season (97.65%) than in the winter and summer months (67.86% and 81.63% respectively; p.001). Private practitioners treated most cases of diarrhea regardless of the season (94.1% in rainy season, 53.6% and 75.5% in winter and summer months respectively). On the other hand, government health facilities treated relatively few cases (3.5%, 17.9%, and 0 respectively). Use of home available fluids increased significantly from 0-39.62% (p.001). So did use of oral rehydration packets 2.7-32%; p.001). The researchers accredited this improvement to educational activities. Women tended to continue breastfeeding and giving other foods to children during diarrheal episodes. Nevertheless there was room for improvement. These results revealed the need for educational efforts to encourage caretakers to use home available fluids and oral rehydration solution and to reorient private practitioners to avoid using drugs and to use oral rehydration therapy.

Analgesic, antipyretic and ulcerogenic activity of Nyctanthes arbor tristis leaf extract.

The leaves of Nyctanthes arbor tristis, besides being used in the treatment of sciatica and arthritis, are advocated for various kinds of fevers and painful conditions by the Ayurvedic physicians. In the present study, the water-soluble portion of an ethanol extract of the leaves was screened for analgesic, antipyretic and ulcerogenic activities. The extract exhibited significant aspirin-like antinociceptive activity but failed to produce morphine-like analgesia. It was also found to possess antipyretic activity against brewer's yeast-induced pyrexia in rats. The extract also produced gastric ulcers following oral administration for six consecutive days in rats. Results of the present study tend to substantiate the use of this plant in fevers and painful conditions by Ayurvedic physicians.

Study of anti-inflammatory activity in the leaves of Nyctanthes arbor tristis Linn.--an Indian medicinal plant.

Nyctanthes arbor tristis Linn. (Harsingar) is widely used as a decoction in the Ayurvedic system of medicine for treatment of sciatica and arthritis, but it has not yet been screened scientifically. In the present study, the water soluble portion of the alcoholic extract of the leaves of Nyctanthes arbor tristis (NAT) was screened for the presence of anti-inflammatory activity. NAT inhibited the acute inflammatory oedema produced by different phlogistic agents, viz. carrageenin, formalin, histamine, 5-hydroxytryptamine and hyaluronidase in the hindpaw of rats. The acute inflammatory swelling in the knee joint of rats induced by turpentine oil was also significantly reduced. In subacute models, NAT was found to check granulation tissue formation significantly in the granuloma pouch and cotton pellet test. Acute and chronic phases of formaldehyde induced arthritis were significantly inhibited. NAT was also found to inhibit the inflammation produced by immunological methods, viz. Freund's adjuvant arthritis and PPD induced tuberculin reaction. Thus anti-inflammatory activity in leaves of Harsingar supports its use in various inflammatory conditions by the followers of the Ayurvedic system of medicine.