Status of free radicals and antioxidants in leprosy patients.

Oxidative stress is a condition associated with an increased rate of cellular damage induced by the oxygen derived oxidants commonly known as reactive oxygen species (ROS). ROS are capable of damaging cellular constituents generated in excess during the chronic, inflammatory, neurodegenerative disease process of leprosy. Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The decreased levels of SOD, glutathione and total antioxidant status in leprosy patients may indicate a degradation of these antioxidant enzymes by free radicals during detoxification processes. The subjects for this study comprises of Normal human volunteers (NHV, n = 20) and treated MB patients (MB, n = 20). The levels of lipid peroxidation products are increased in MB Patients (*P < 0.001). SOD (**P < 0.0001) and glutathione levels (***P < 0.0001) decreased in MB Patients in comparision with normal human volunteers. The present study of estimation of antioxidants conclude that the free radical activity was increased and the total antioxidant status was decreased in all MB patients, indicating that there was an oxidative stress even after the treatment with MDT. The decreased levels of SOD, glutathione indicate a link between oxidative stress and leprosy. Since the MB patients are unable to produce sufficient amount of antioxidant to cope up with the increased oxidative stress in them. Providing nutritional supplementation may present a novel approach for fast recovery. Administration of exogenous antioxidants like vitamin C, tocopherols would prevent tissue damage and make the patient therapeutically benefited.

Oxidative stress and anti-oxidant status in leprosy patients.

Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The purpose of this study was to investigate the serum lipid peroxidation products, serum LDH and important free radical scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. The subjects for this study were normal human volunteers (NHVs, n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1, n=18), MB patients under treatment (MB2, n=19), and MB patients released from treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product, malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2, MB3) patients, and both gradually decreased with clinical improvement following MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in comparison with NHVs. They gradually increased with clinical improvement with MDT. There was no significant variation of these parameters in PB leprosy patients in comparison with healthy volunteers. High free radical activity and low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate that there is an oxidative stress in MB cases, irrespective of the treatment status and suggest a suitable anti-oxidant therapy to prevent possible tissue injury.

Assessment of antioxidant activity of some antileprotic drugs.

DPPH (alpha,alpha-diphenyl-beta-picryl hydrazyl) (CAS 217-591-8), a stable free radical can be used to determine the antioxidant activity (AOA) of some drugs. In the present study the DPPH method was used for the first time to test AOA of dapsone (CAS 80-08-0), clofazimine (CAS 2030-63-9) and rifampicin (CAS 13282-42-1) in vitro and deproteinated blood method. Ascorbic acid (CAS 50-81-7) was used as a control in the study, which showed concentration-dependent antioxidant activity. Rifampicin showed a per se effect but it showed concentration dependent decrease in the DPPH absorbance. Ascorbic acid, dapsone and rifampicin showed DPPH scavenging activity both in vitro and deproteinated blood method. Clofazimine did not have any influence on DPPH. This method may be extended to different drugs for testing their AOA in biological fluids.

Influence of rice bran oil on serum lipid peroxides and lipids in human subjects.

To study the effect of rice bran oil (RBO) on serum lipids and lipid peroxides in human volunteers. Nine healthy volunteers, aged between 42 to 57 years were given 75 ml of RBO thrice daily as the cooking medium with break fast, lunch and dinner for a period of 50 days. At the beginning and at the end of 50 days, 5 ml of blood were drawn from an ante cubital vein. Serum lipids and lipid peroxides levels were estimated from the blood sample. There was a significant decrease in the levels of lipid peroxides, triglycerides, LDL, VLDL, and total cholesterol in human volunteers who switched over to RBO. RBO has evidently antioxidant and antilipidemic activities in human subjects.

Screening methods for antiasthmatic agents.

Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This review intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods. Detailed experimental methods have been included with appropriate literature citations.

Antinociceptive and anti-inflammatory activity of carumbelloside-I isolated from Caralluma umbellata.

The phytochemical study using Caralluma umbellata (Asclepiadaceae) whole plant allowed the isolation of a novel pregnane glycoside named carumbelloside-I (3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-3beta,14beta -dihydroxypregn-5-en-20-one). Carumbelloside-I was evaluated for both antinociceptive activity and anti-inflammatory activity. The antinociceptive activity was evaluated in mice using the writhing test method, while the anti-inflammatory activity was evaluated in rats using the paw edema test with carrageenin. Carumbelloside-I has significant antinociceptive action. It has no anti-inflammatory activity.

Antinociceptive and anti-inflammatory activity of a flavonoid isolated from Caralluma attenuata.

Luteolin-4'-O-neohesperidoside, i.e. luteolin-4'-O-[alpha-(L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside)] has significant anti-inflammatory action. It is more potent than ibuprofen. Its antinociceptive activity is less pronounced when compared with its anti-inflammatory activity.

Characterization of leprosy based on the nasal lipid profile.

While extracting the M. leprae from the nasal flushings of leprosy patients it was found that these organisms were trapped in the waxy layer, between the aqueous and the chloroform layers. Thin layer chromotography (TLC) analysis of this layer, using chloroform-methanol-water system, revealed different spots when sprayed with acid alcohol and heated at 160 degrees C. The TLC profile of lipids of lepromatous and borderline (MB according to the WHO terminology) leprosy patients was distinctly different from that of tuberculoid leprosy patients and normal human volunteers. A simple, economical and fast procedure to characterize patients belonging to different spectra has been developed.

Disposition of rifampicin following intranasal and oral administration.

Leprosy is transmitted by dissemination of M.leprae which are lodged in the nose of the patients suffering from multibacillary (MB) type of the disease. Rifampicin, a potent bactericidal antileprotic drug is given orally to the patients with a view to make the infective cases non-infective. Earlier work by us has shown that intranasal administration of rifampicin helps in reducing the M.leprae load in the nose much faster than after conventional oral administration. In the present study, rifampicin concentrations in plasma/urine/nasal wash of healthy volunteers following oral and intranasal administration were determined. Following intranasal administration, rifampicin was not detectable in plasma and high concentrations were measured in the nasal wash. Following oral administration, rifampicin was not detectable in the nasal wash indicating that enough antibiotic levels are not available for clearing M.leprae from nose.

Tissue distribution and deposition of clofazimine in rat following subchronic treatment with or without rifampicin.

Tissue distribution and deposition characteristics of clofazimine (CAS 2030-63-9), an antileprotic drug in rats have been investigated following controlled sub-chronic administration (p.o.) for a period of 1-2 months. The drug was administered alone at a dose of 20 mg/kg body weight and in combination with rifampicin (CAS 13292-46-1) (20 mg/kg p.o.). Various tissues (liver, lung, spleen, small intestine, brain, heart, kidney, skin, stomach and subcutaneous fat) were analyzed for clofazimine in all the treated groups. High levels (range 0.9-3.6 mg/g of wet tissue) were observed in tissues having reticuloendothelial components. In other tissues the levels were relatively lower (range 3-114 micrograms/g of wet tissue). Histopathological studies revealed that clofazimine is deposited in many tissues in the form of reddish-orange crystals. Concomitant treatment with rifampicin did not significantly alter tissue distribution or deposition profile of clofazimine nor did it influence the histopathology.

Role of rifampin and clofazimine ointments in the treatment of leprosy.

The use of rifampin and clofazimine ointments alone and in combination over the patches of tuberculoid patients had a beneficial effect. In combination (rifampin and clofazimine), erythema, inflammation, and edema are considerably reduced. For some of the cases with a recent appearance of a patch, the patch completely disappeared. It is suggested that topical therapy with rifampin and clofazimine ointments would be economical and beneficial in tuberculoid leprosy.

New approach to curb the transmission of leprosy.

The effect of local treatment of nose of lepromatous type of patients with different formulations of rifampicin nasal drops/sprays was investigated in a large number of patients. The preparations were either sprayed or instilled into the nostrils after flushing the nostrils with normal saline at 37 degrees C. It was observed that 10 mg/ml of rifampicin was effective in reducing the BI and MI to zero in nose in seven days in majority of the patients. No untoward effect was seen in any of the patients. It is suggested that nasal sprays/drops may be able to prevent the transmission of hanseniasis, as nose is recognised to be an important portal of exit of M. leprae. Further when rifampicin drops/sprays are used as soon as the diagnosis is made, the nasal deformity may be prevented. It is believed that local treatment along with systemic therapy would go a long way in controlling the transmission of hanseniasis.

New approach to curb the transmission of leprosy

O efeito do tratamento local do nariz de paciente do tipo lepromatoso com diferentes formulaçöes de rifampicina em gotas ou "sprays" nasais, foi investigado em um grande número de pacientes. As preparaçöes foram ou aspergidas ou instiladas dentro das narinas depois de sua limpeza por jato com soluçäo salina normal a 37-C. Observou-se que 10 mg/ml de rifampicina eram eficazes na reduçäo do BI e do MI a zero no nariz em sete dias na maioria dos pacientes. Näo foi visto efeito desagradável em qualquer dos paciente. Sugere-se que "sprays"/gotas nasais possam prevenir a transmissäo da hanseníase, uma vez que o nariz é reconhecido ser uma importante porta de saida de M. leprae. Além disso a deformidade nasal pde ser prevenida quando a rifampicina "sprays"/gotas é usada täo logo o diagnóstico é feito. Acredita-se que o tratamento local juntamente com a terapia sistêmica contribuiriam muito no controle da transmissäo da hanseníase

How much non-infectious are the "non-infectious" lepromatous leprosy patients?

Nose forms an important site at which the M. leprae in lepromatous leprosy (LL) patients lodge and multiply. Nose forms an important reservoir for M. leprae, from where they may be transmitted to healthy contacts. Inspite of realizing the above fact, nose does not normally receive due importance during the chemotherapy of leprosy. LL patients, after regular treatment with dapsone or rifampin for about 20 wks and 3 wks respectively are normally considered non-infectious. From the present investigation it is clear that local treatment of the ones with a bactericidal agent should perhaps be necessary during chemotherapy of LL patients to make them non-infectious and to control the transmission of the disease.

Jala Neti a yoga technique for nasal comfort and hygiene in leprosy patients

The technique 'Jala Neti' as described in yoga is a general hygienic procedure to cleanse the nostrils effectively with a normal saline. The above mentioned technique was tried in three leprosy centres namely Jammikunt, Huzurabad and Warangal in Andhra Pradesh, India and was found to be acceptable to patients of leprosy. The technique has been found to be superior to the conventional method recommended to cleanse the nostrils in leprosy patients.