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Biomedical subjects

P K Murthy

Publications and source records attributed to P K Murthy.

At least 37 records · Page 2Linked to original sources

Brugia malayi in Mastomys coucha: establishment in immunosuppressed animals.

Investigations on various aspects of human filariasis using target filarial parasite, Brugia malayi is jeopardised to a great extent due to its prolonged incubation period and poor harvest from the existing experimental animal models. To obviate these difficulties it was decided to establish B. malayi infection in immunosuppressed Mastomys coucha. Cortisone, a well-known immunosuppressant, was used at 10-mg/kg dose level subcutaneously in two courses each of 5 days duration. The first course was administered 1 week before and the second, 1 week after infective exposure. Mastomys were exposed either with 100 or 200 L3 each. Untreated age-matched animals were also exposed simultaneously. The minimum prepatent period was observed to be 90.7 days in immunosuppressed animals exposed to 200 L3. The course of microfilaraemia in immunosuppressed and control animals was identical up to 180 days of observation period. However, the adult worm recovery from the former group of mastomys was higher. It is surmised that exposure with B. malayi L3 in immunosuppressed mastomys would be of great advantage in getting larger harvests of adult worms of B. malayi.

Animals↗

Brugia malayi in Mastomys coucha: establishment in immunosuppressed animals.

Investigations on various aspects of human filariasis using target filarial parasite, Brugia malayi is jeopardised to a great extent due to its prolonged incubation period and poor harvest from the existing experimental animal models. To obviate these difficulties it was contemplated to establish B. malayi infection in immunosuppressed Mastomys coucha. Cortisone, a well known immunosuppressant, was used at 10 mg/kg dose level subcutaneously in two courses each of 5 days duration. The first course was administered 1 week before and the second, a week after infective exposure. Mastomys were exposed either with 100 or 200 infective larvae (L3) each. Untreated age-matched animals were also exposed simultaneously. The minimum prepatent period was observed to be 90.7 days in immunosuppressed animals exposed to 200 L3. The course of microfilaraemia in immunosuppressed and control animals was identical up to 180 days of observation period. However, the adult worm recovery from the former group of Mastomys was higher. It is surmised that exposure with B. malayi L3 in immunosuppressed Mastomys would be of great advantage in getting larger harvests of adult worms of B. malayi.

Animals↗

Fate of infective larvae of Brugia malayi in the peritoneal cavity of Mastomys natalensis and Meriones unguiculatus.

The fate of intraperitoneally inoculated infective third-stage larvae (L3) of the nematode Brugia malayi Lichtenstein and the status of the peritoneal macrophage function were investigated in the susceptible rodent hosts Mastomys natalensis Roberts and Meriones unguiculatus Milne-Edwards (jird). Jirds and M. natalensis were inoculated intraperitoneally with 125 and 250 L3 and the worm burden and peritoneal macrophage function in the two species were compared at different days post-inoculation (DPI). None of the infected M. natalensis had adult worms in the peritoneal cavity; very few degenerating L3 surrounded by peritoneal cells were recovered 7 and 15 DPI. In contrast, all the infected jirds showed the parasite in different stages of development and the worm burden at different days PI was more in 250 L3 dose group than in 125 L3 dose group. The phagocytic function of peritoneal macrophages of normal M. natalensis was twice higher than that of jirds. This function was found significantly suppressed in both host species at 15 DPI; at 35 DPI, the activity was still at this low level in the jird, while that in M. natalensis reverted to uninfected age- and sex-matched control levels. These findings demonstrate that the peritoneal environment of M. natalensis is not conducive to the development of B. malayi and this is probably related to high macrophage activity in the peritoneum of this host compared to that found in the jird.

Animals↗

Brugia malayi in Mastomys natalensis: influence of immunostimulators on exertion of antifilarial activity of diethylcarbamazine.

The effect of immunopotentiators (Freund's complete adjuvant and CDRI Compound no. 84/201) has been evaluated on exertion of antifilarial activity of diethylcarbamazine (DEC) at different dose levels in Mastomys natalensis experimentally infected with Brugia malayi. DEC alone exhibited dose dependent micro- as well as macrofilarial action. In combination with immunomodulators, activity of DEC was significantly enhanced even at a lower dose level (12.5 mg/kg). However at higher dose level (> 25 mg/kg) of the drug along with immunostimulator the adulticidal activity was significantly reduced. Nevertheless, immunopotentiators themselves displayed certain amount of antifilarial action (34-38% macrofilaricidal).

Adjuvants, Immunologic↗

Brugia malayi in Mastomys natalensis: efficacy of mebendazole in combination with Freund's complete adjuvant.

The chemotherapeutic efficacy of mebendazole given in combination with Freund's complete adjuvant (FCA) against Brugia malayi in multimammate rat was evaluated. Animals treated with mebendazole, orally at 200 mg/kg x 5 consecutive days along with FCA given subcutaneously (s.c.) on day -10, day 0 and day +15 of the drug treatment killed 48.51% of the adult worms. This drug given alone at the same regimen and by the same route showed only 18.7% mortality rate on adults. Mebendazole given intraperitoneally along with FCA given s.c., however, was four times more efficacious as filaricide than mebendazole alone. Nevertheless, the animals receiving FCA alone also revealed 23.5% mortality rate of adult worms. The animals receiving a combination therapy or FCA alone showed significant increase in antibody titre to the filariae which however decreased in the later stages. No enhancement of antibody level could be detected in animals treated with mebendazole alone. The non-specific immunopotentiation induced by FCA appeared to play a major role in enhancing the activity of mebendazole.

Administration, Oral↗

On estimating fertility using first and second order births.

"An attempt has been made to present two regression equations for estimating total fertility rate from the birth order data. While one of the equations has been derived from the longitudinal data of Malaysia another has been obtained from cross sectional data on Mother's total fertility rate...and births of orders one and two. These equations are used to estimate the [total fertility rate] for the districts of [Uttar Pradesh, India,] which are quite close to the estimates obtained by using other methods."

Asia↗

Susceptibility of Mastomys natalensis to Brugia malayi following pretreatment with antifilarials.

Mastomys natalensis pretreated with diethylcarbamazine (DEC), levamisole or centperazine were exposed to the standard inoculum of infective larvae of Brugia malayi. Percentage 'take' of infection, duration of prepatent period, course of microfilaraemia and number of adult worms recovered were compared with those of untreated infected Mastomys (control). DEC and centperazine did not alter the 'take' (DEC/centperazine: 100%; control: 88.24%) and the average prepatent period (DEC: 105.44 days; centperazine: 105.18 days, control: 109.20 days). In levamisole pretreated animals on the other hand, the 'take' was much lower (68.18%) with extended prepatent period (125.87 days). However, unlike centperazine and control, the course of microfilaraemia was identical in DEC and levamisole pretreated animals. The average adult worm recovery was significantly high in centperazine pretreated animals being 14.09 as against 8.12, 7.46 and 8.42 in DEC, levamisole pretreated and control animals, respectively.

Animals↗

Evaluation of filarial skin test with Brugia malayi larval antigen in the field.

To obtain comparable and reproducible results by filaria skin test with B. malayi larval antigen, standard procedure has been evolved. Antigen protein of 2 micrograms per test, injected intracutaneously, was found optimum for positive skin reaction. The reaction ratio based on increase of wheal area by 2 times or more was found to be statistically significant for interpreting positive results. However, in larger field trials, the simpler measurement of increase of wheal diameter by 1 1/2 times or more was found to be equally reliable. Patients treated with diethylcarbamazine citrate, antihistaminics and anti-inflammatory drugs are likely to be unresponsive to filarial antigen and will yield incorrect information.

Animals↗

Circadian periodicity in microfilarial counts.

We propose a second-order harmonic model to describe circadian periodicity in the 24-h cycle of microfilarial counts. Rhesus monkeys (Macaca mulatta) were infected with Brugia malayi. Definite evidence of circadian periodicity was found in the microfilarial counts. The estimates of the parameters, periodicity indices and peak hours were determined.

Analysis of Variance↗

Brugia malayi: status of host during different stages of infection.

The status of glycogen, protein, lipid components, lipid peroxides and a few enzymes of energy metabolism was studied in liver of Mastomys natalensis during the development of Brugia malayi infection. Glycogen and lipid contents were decreased during the patent phase of infection while total protein was slightly altered in latent animals. Phospholipid and triglyceride contents declined at prepatent and patent phase of infection. The levels of lactate and malate dehydrogenases, as well as of adenosine triphosphatases (Na+K+, Mg2+, Ca2+), were significantly elevated and monoamine oxidase activity was decreased at patent phase of infection, while succinic dehydrogenase remained unaltered. The lipid peroxide formation was enhanced in liver during the development of filarial infection.

Adenosine Triphosphatases↗

Comparative analysis of surface components of adult, micro-filariae and infective larvae of Brugia malayi.

A comparative analysis of surface proteins of adult, microfilariae and infective larvae of Brugia malayi, the human filarial parasite, has been carried out using IODOGEN (1,3,4,6-tetrachloro-3,alpha 6 alpha-diphenyl-glycoluril) and lactoperoxidase methods. SDS-polyacrylamide gel electrophoretic and autoradiographic analyses revealed the presence of 9 proteins (15-200 kDa) in adults, while microfilariae and infective larvae showed 8 and 6 proteins (15-120 kDa), respectively. The pattern of proteins radiolabelled by IODOGEN method was very similar to that of proteins labelled by the lactoperoxidase method. Since these proteins are released by the protease treatment of whole parasites, they are likely to be present on the surface of the parasite.

Animals↗

Efficacy of a substituted methyl benzimidazole carbamate against developing and adult helminth parasites.

The efficacy of a substituted methyl benzimidazole carbamate, methyl 5(6)-[4-N-(2-pyridyl)] piperazino carbamoyl benzimidazole-2-carbamate, was assessed against larval and adult forms of Ancylostoma ceylanicum (hookworm), Nippostrongylus brasiliensis (trichostrongylid), Hymenolepis nana (tapeworm) and Brugia malayi (filariid) in experimentally-infected animals. The compound was found to have high efficacy against the developing stages (L3, L4, L5) of A. ceylanicum in hamsters at a single dose of 12.5 mg kg-1, against larvae of N. brasiliensis at 17.5 mg kg-1 and against cysticercoids of Hymenolepis nana at 100 mg kg-1 daily for 3 days given per os (p.o.) or intraperitoneally (i.p.). All the stages of B. malayi in Mastomys were killed when the compound was given i.p. at a dose of 6.25 mg kg-1 for 5 consecutive days. A dose of 6.25 mg kg-1 eliminated all adult A. ceylanicum from infected hamsters, 100 mg kg-1 resulted in complete removal of Syphacia obvelata adults from 63.6% of infected mice, 25 mg kg-1 X 5 dose eliminated 100% of adult B. malayi from infected Mastomys and a single 50 mg kg-1 dose expelled all H. nana adults from infected rats.

Ancylostoma↗