Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its ro... more Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its role in the reported interaction between grapefruit juice and nifedipine has been determined in vivo in humans. Eight healthy volunteers were given in random order 10 mg nifedipine orally, either alone or with 200 ml double strength grapefruit juice, or with 400 mg quercetin. The area under the plasma concentration‐time curve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml−1 h) was increased significantly (P < 0.01) compared with the AUC when nifedipine was given alone (mean 218 ng ml−1 h). The time to peak plasma concentration for nifedipine with grapefruit juice (1.5 h) was also increased (P < 0.05) compared with control (0.5 h) suggesting delayed absorption. Although quercetin delayed the time to peak nifedipine concentration (1.3 h) it did not alter the AUC of either the parent drug (mean 209 ng ml−1 h) or its first‐pass metabolite. The results suggest that quercetin d...
ELEMENTS OF CRIME AND GENERAL EXCEPTIONS OF CRIMINAL LIABILITIES , 2024
An act, default or conduct prejudicial to the community, the commission of which the law renders ... more An act, default or conduct prejudicial to the community, the commission of which the law renders the person responsible liable to punishment by a fine or imprisonment in special proceedings. This definition it was propounded by Osborn G.p on his concise law dictionary 5 th Ed. But also according to the instructions of the Question there two basis formation or elements of crime which are Actus reus and men's rea. I start with Actus reus Actus reus Is Latin words. Actus simply means an act and reus is that prohibited by law. Therefore actus reus may be described as such result of human conduct as the law seeks to prevent. The word conduct here covers both acts and omissions. It may be accomplished by an action, by threat of action, or exceptionally, by an omission to act. For example, the act of A striking B might suffice, or a parent's failure to give
Transactions of the Royal Society of Tropical Medicine and Hygiene, Jun 7, 2016
Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved pati... more Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved patient-adapted treatments are needed. The Leishmaniasis East Africa Platform (LEAP) was created in 2003 to strengthen clinical research capacity, serve as a base for training, and evaluate and facilitate implementation of new treatments. Major infrastructure upgrades and personnel training have been carried out. A short course of Sodium Stibogluconate and Paramomycin (SSG&PM) was evaluated and is now first-line treatment in the region; alternative treatments have also been assessed. LEAP can serve as a successful model of collaboration between different partners and countries when conducting clinical research in endemic countries to international standards.
This study was an open evaluation of the efficacy and safety of Ketoconazole, 15 mg/kg/day orally... more This study was an open evaluation of the efficacy and safety of Ketoconazole, 15 mg/kg/day orally for 3 weeks in 7 evaluable patients with Visceral Leishmaniasis in Kenya. Of all the seven patients who received ketoconazole, none had appreciable clearance of parasites from the splenic aspirate smears that were microscopically examined. All the splenic aspirate cultures done on these patients in the three weeks remained positive for leishmania parasites. Splenic sizes of these patients generally remained unchanged throughout the study period. The mean haemoglobin at the start of treatment was not different from that at the end of treatment. Liver function tests throughout treatment remained unchanged, i.e. within normal limits. It is concluded that Ketoconazole, 15 mg/kg/day orally given to these patients was not effective as an antileishmania drug although there was a one log drop in the parasite load. However, no serious side effect were noted in all of the patients during treatment.
SummaryAdherent mononuclear cells (monolayer), when co‐cultured with autologous peripheral blood ... more SummaryAdherent mononuclear cells (monolayer), when co‐cultured with autologous peripheral blood eosinophils isolated from patients treated for Schistosoma mansoni infections, enhanced the eosinophil‐mediated killing of antibody coated schistosomula. The monolayer increased the activity of the eosinophils by 225%, and was observed in 80% of the patients studied. Heat labile factors other than complement, present in immune serum, further enhanced the ability of eosinophils to kill schistosomula in the presence of the monolayer. On their own the adherent cells did not mediate obvious damage to the parasite. Eosinophils that had been pre‐incubated with the monolayer (100 mins) and tested separately, killed equal numbers of schistosomula as in the co‐culture assay; this excludes the possibility of concurrent schistosomula cytotoxicity by the two cell populations. The ability of the monolayer to activate eosinophils was not altered by inhibitors of protein synthesis. The monolayer was la...
The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquin... more The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquinoline) (WR6026) in the treatment of 16 patients with kala azar was evaluated. The first 8 patients received therapy for 2 weeks at a dosage of 0.75-1.00 mg/(kg.d); 1 patient was cured, and in regard to the other 7, a 1-logarithm decrease in the number of splenic parasites and clinical improvement were noted. The next 8 patients received therapy for 4 weeks at the same daily dosage (1 mg/[kg.d]); 4 were cured, and for the other 4, 1- to 2-log decreases in the number of parasites and clinical improvement (in regard to weight, liver and spleen size, hemoglobin level, and leukocyte count) were noted. The therapy was associated with minimal toxicity; adverse effects included gastrointestinal distress, headache, and methemoglobinemia. The fact that one-half of the patients were cured indicates that future trials with longer regimens and higher dosages are warranted and should include patients for whom existing treatment methods have failed.
SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern ... more SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, defini...
I. Administrative Law-An Overview: Issues and prospects *Introduction Concept, Definition scope a... more I. Administrative Law-An Overview: Issues and prospects *Introduction Concept, Definition scope and recent *trends in Administrative Law *Role of the Constitution and administrative Law, *Constitutional Provisions like Separation of Power *Rule of Law and *Droit Administrative. II. Classification of Administrative Power *Rules Making Power *Adjudicatory Power *Administrative Powers III. Delegated Legislation and its Control *Delegated legislation, factors leading to delegated legislation *Restraints on delegation of legislative power *Control over delegated legislation.
Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its ro... more Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its role in the reported interaction between grapefruit juice and nifedipine has been determined in vivo in humans. Eight healthy volunteers were given in random order 10 mg nifedipine orally, either alone or with 200 ml double strength grapefruit juice, or with 400 mg quercetin. The area under the plasma concentration‐time curve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml−1 h) was increased significantly (P < 0.01) compared with the AUC when nifedipine was given alone (mean 218 ng ml−1 h). The time to peak plasma concentration for nifedipine with grapefruit juice (1.5 h) was also increased (P < 0.05) compared with control (0.5 h) suggesting delayed absorption. Although quercetin delayed the time to peak nifedipine concentration (1.3 h) it did not alter the AUC of either the parent drug (mean 209 ng ml−1 h) or its first‐pass metabolite. The results suggest that quercetin d...
ELEMENTS OF CRIME AND GENERAL EXCEPTIONS OF CRIMINAL LIABILITIES , 2024
An act, default or conduct prejudicial to the community, the commission of which the law renders ... more An act, default or conduct prejudicial to the community, the commission of which the law renders the person responsible liable to punishment by a fine or imprisonment in special proceedings. This definition it was propounded by Osborn G.p on his concise law dictionary 5 th Ed. But also according to the instructions of the Question there two basis formation or elements of crime which are Actus reus and men's rea. I start with Actus reus Actus reus Is Latin words. Actus simply means an act and reus is that prohibited by law. Therefore actus reus may be described as such result of human conduct as the law seeks to prevent. The word conduct here covers both acts and omissions. It may be accomplished by an action, by threat of action, or exceptionally, by an omission to act. For example, the act of A striking B might suffice, or a parent's failure to give
Transactions of the Royal Society of Tropical Medicine and Hygiene, Jun 7, 2016
Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved pati... more Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved patient-adapted treatments are needed. The Leishmaniasis East Africa Platform (LEAP) was created in 2003 to strengthen clinical research capacity, serve as a base for training, and evaluate and facilitate implementation of new treatments. Major infrastructure upgrades and personnel training have been carried out. A short course of Sodium Stibogluconate and Paramomycin (SSG&PM) was evaluated and is now first-line treatment in the region; alternative treatments have also been assessed. LEAP can serve as a successful model of collaboration between different partners and countries when conducting clinical research in endemic countries to international standards.
This study was an open evaluation of the efficacy and safety of Ketoconazole, 15 mg/kg/day orally... more This study was an open evaluation of the efficacy and safety of Ketoconazole, 15 mg/kg/day orally for 3 weeks in 7 evaluable patients with Visceral Leishmaniasis in Kenya. Of all the seven patients who received ketoconazole, none had appreciable clearance of parasites from the splenic aspirate smears that were microscopically examined. All the splenic aspirate cultures done on these patients in the three weeks remained positive for leishmania parasites. Splenic sizes of these patients generally remained unchanged throughout the study period. The mean haemoglobin at the start of treatment was not different from that at the end of treatment. Liver function tests throughout treatment remained unchanged, i.e. within normal limits. It is concluded that Ketoconazole, 15 mg/kg/day orally given to these patients was not effective as an antileishmania drug although there was a one log drop in the parasite load. However, no serious side effect were noted in all of the patients during treatment.
SummaryAdherent mononuclear cells (monolayer), when co‐cultured with autologous peripheral blood ... more SummaryAdherent mononuclear cells (monolayer), when co‐cultured with autologous peripheral blood eosinophils isolated from patients treated for Schistosoma mansoni infections, enhanced the eosinophil‐mediated killing of antibody coated schistosomula. The monolayer increased the activity of the eosinophils by 225%, and was observed in 80% of the patients studied. Heat labile factors other than complement, present in immune serum, further enhanced the ability of eosinophils to kill schistosomula in the presence of the monolayer. On their own the adherent cells did not mediate obvious damage to the parasite. Eosinophils that had been pre‐incubated with the monolayer (100 mins) and tested separately, killed equal numbers of schistosomula as in the co‐culture assay; this excludes the possibility of concurrent schistosomula cytotoxicity by the two cell populations. The ability of the monolayer to activate eosinophils was not altered by inhibitors of protein synthesis. The monolayer was la...
The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquin... more The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquinoline) (WR6026) in the treatment of 16 patients with kala azar was evaluated. The first 8 patients received therapy for 2 weeks at a dosage of 0.75-1.00 mg/(kg.d); 1 patient was cured, and in regard to the other 7, a 1-logarithm decrease in the number of splenic parasites and clinical improvement were noted. The next 8 patients received therapy for 4 weeks at the same daily dosage (1 mg/[kg.d]); 4 were cured, and for the other 4, 1- to 2-log decreases in the number of parasites and clinical improvement (in regard to weight, liver and spleen size, hemoglobin level, and leukocyte count) were noted. The therapy was associated with minimal toxicity; adverse effects included gastrointestinal distress, headache, and methemoglobinemia. The fact that one-half of the patients were cured indicates that future trials with longer regimens and higher dosages are warranted and should include patients for whom existing treatment methods have failed.
SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern ... more SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, defini...
I. Administrative Law-An Overview: Issues and prospects *Introduction Concept, Definition scope a... more I. Administrative Law-An Overview: Issues and prospects *Introduction Concept, Definition scope and recent *trends in Administrative Law *Role of the Constitution and administrative Law, *Constitutional Provisions like Separation of Power *Rule of Law and *Droit Administrative. II. Classification of Administrative Power *Rules Making Power *Adjudicatory Power *Administrative Powers III. Delegated Legislation and its Control *Delegated legislation, factors leading to delegated legislation *Restraints on delegation of legislative power *Control over delegated legislation.
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