Drug resistance in malaria

Ever since the discovery of the first case of chloroquine resistance along the Thai-Combodian border in the late 1950s, Southeast Asia has played an important role as a focus for the development of drug resistance in Plasmodium falciparum. Although the first case of quinine resistance had been reported much earlier from South America, the onset of chloroquine resistance marked the beginning of a new chapter in the history of malaria in Southeast Asia and by 1973 chloroquine finally had to be replaced by the combination of sulphadoxine and pyrimethamine (SP) as first line drug for the treatment of uncomplicated malaria in Thailand and more than 10 African countries have also switched their first line drug to SP. In 1985, eventually SP was replaced by mefloquine. The rapid development of resistance to this new drug leads to the introduction of artemisinin as a combination drug in the mid-1990s. It is mandatory to mention here that therapeutic regimens for prevention and treatment of chloroquine-resistant P. falciparum are associated with higher costs and side-effects compared to chloroquine. Additionally, some of these alternative treatments are associated with more side-effects, take longer time for cure and are more difficult to comply with than chloroquine. Urgent efforts are needed to identify effective, affordable, alternative antimalarial regimens. Molecular markers for antimalarial resistance have been identified, including pfmdr-1 and pfcrt polymorphisms associated with chloroquine resistance and dhfr and dhps polymorphisms associated with SP resistance. Polymorphisms in pfmdr-1 may also be associated with resistance to chloroquine, mefloquine and artemisinin. Use of such genetic information for the early detection of resistance foci and future monitoring of drug resistant malaria is a potentially useful epidemiological tool, in conjunction with the conventional in vitro and in vivo drug sensitivity assessments. The purpose of this review is to describe the state of knowledge regarding drug resistant malaria and to outline the changing patterns of drug resistance including its determinants, current status in diverse geographical areas, molecular markers and their implications to limit the advent, spread and intensification of drug resistant malaria.     

"Were-wolf" cutaneous tuberculosis

Lupus vulgaris is a variant of cutaneous tuberculosis. Its more destructive and mutilating clinical forms have become rarer in consonance of a general decline of cutaneous tuberculosis. It is rarely seen now in developed countries due to stringent control measures, improved quality of living and effective therapeutic regimens. Misdiagnosis, neglect, or late diagnosis may result in severe, ulcerative and mutilating "wolf eaten" skin lesions.This paper describes four such cases of "were-wolf" cutaneous tuberculosis. Early diagnosis and treatment is important to prevent much of the disfigurement.     

Improved cardioprotection using a novel stepwise ischemic preconditioning protocol in rabbit heart

Background

The current commonly used cardiac ischemic preconditioning (IPC) protocol, involving three 5-min cycles of ischemia–reperfusion (I/R), may not be clinically beneficial because of its acutely deleterious effects on hemodynamics. This study attempted to assess the effects of a novel stepwise IPC scheme on cardiac function, infarct size, and arrhythmogenesis in a rabbit model of prolonged I/R.

Methods

Anesthetized open-chest rabbits were subjected to 60-min occlusion of a proximal branch of the left coronary artery followed by 180-min reperfusion. Animals were divided into five groups (n = 6 each): (1) control group (no IPC); (2) 2-min IPC group (three cycles of 2-min IPC); (3) 5-min IPC group (three cycles of 5-min IPC); (4) 10-min IPC group (three cycles of 10-min IPC); and (5) stepwise IPC group (2-, 5-, and 10-min I/R).

Results

Compared with control group, 2-, 5-, and 10-min IPC decreased arrhythmia score by 16%, 67%, and 33%, respectively. Remarkably, stepwise IPC resulted in a 78% reduction of arrhythmias. Stepwise IPC also produced the least ventricular infarct size when compared with 2-, 5-, and 10-min IPC groups (16.4% versus 39.3%, 28.1%, and 38.5%, P < 0.05).

Conclusions

These results suggest that stepwise IPC has better cardioprotective effects against prolonged I/R injury and may serve as an acceptable approach to clinical revascularization procedures on the heart, including catheter-based and surgical approaches.     

Primary Malignant Melanoma of Maxillary Gingiva

Malignant melanoma of maxillary gingiva is a rare clinical entity. Mucosal melanoma is more aggressive than cutaneous form and carries comparatively poorer prognosis. High index of suspicion is required for diagnosing malignant melanoma of oral cavity. Any pigmented lesion in the oral cavity should be taken seriously by the clinician.     

Enhancement of Anticorrosive Performance of Cardanol Based Polyurethane Coatings by Incorporating Magnetic Hydroxyapatite Nanoparticles

The present investigation demonstrates renewable cardanol-based polyol for the formulation of nanocomposite polyurethane (PU) coatings. The functional and structural features of cardanol polyol and nanoparticles were studied using FT-IR and 1H NMR spectroscopic techniques. The magnetic hydroxyapatite nanoparticles (MHAPs) were dispersed 1–5% in PU formulations to develop nanocomposite anticorrosive coatings. An increase in the strength of MHAP increased the anticorrosive performance as examined by immersion and electrochemical methods. The nanocomposite PU coatings showed good coating properties, viz., gloss, pencil hardness, flexibility, cross-cut adhesion, and chemical resistance. Additionally, the coatings were also studied for surface morphology, wetting, and thermal properties by scanning electron microscope (SEM), contact angle, and thermogravimetric analysis (TGA), respectively. The hydrophobic nature of PU coatings increased by the addition of MHAP, and an optimum result (105°) was observed in 3% loading. The developed coatings revealed its hydrophobic nature with excellent anticorrosive performance.