Human genetics indicate that kisspeptin and neurokinin B (NKB) signaling are necessary for generating pulsatile LH release and therefore for initiation of puberty and maintaining gonadal function. In the present study, male monkeys were employed to examine 1) whether activation of the NKB receptor (NK3R) is associated with GnRH release, and 2) hypothalamic localization of these peptides using immunofluorescence histochemistry. Agonadal juveniles, in which pituitary responsiveness to GnRH was heightened by GnRH priming, were employed to indirectly examine GnRH-releasing actions of NK3R and kisspeptin receptor agonists by tracking LH after their i.v. injection. Castrated adults were used for immunohistochemistry. Single i.v. injections of NKB or senktide (an NK3R agonist) elicited robust LH discharges that were abolished by GnRH receptor antagonism (acyline) confirming the ligands' hypothalamic action. Intermittent infusion of senktide (1-min pulse every hour for 4 h), in contrast to that of kisspeptin, failed to sustain pulsatile GnRH release. Repetitive senktide injections did not compromise the GnRH-releasing action of kisspeptin. NKB and kisspeptin were colocalized in perikarya of the arcuate nucleus and in axonal projections to the median eminence, confirming earlier findings in sheep. These results are consistent with the human genetics, and indicate that although brief activation of NK3R stimulates GnRH release, repetitive stimulation of this pathway, in contrast to that of kisspeptin receptor, fails to sustain pulsatile GnRH release. In addition, the data provide a platform for future elucidation of the interactions between NKB and kisspeptin that are required for generating pulsatile GnRH release in primates.

Puberty in primates is timed by 2 hypothalamic events: during late infancy a decline in pulsatile GnRH release occurs, leading to a hypogonadotropic state that maintains quiescence of the prepubertal gonad; and in late juvenile development, pulsatile GnRH release is reactivated and puberty initiated, a phase of development that is dependent on kisspeptin signaling. In the present study, we determined whether the arrest of GnRH pulsatility in infancy was associated with a change in kisspeptin expression in the mediobasal hypothalamus (MBH). Kisspeptin was determined using immunohistochemistry in coronal hypothalamic sections from agonadal male rhesus monkeys during early infancy when GnRH release as reflected by circulating LH concentrations was robust and compared with that in juveniles in which GnRH pulsatility was arrested. The distribution of immunopositive kisspeptin neurons in the arcuate nucleus of the MBH of infants was similar to that previously reported for adults. Kisspeptin cell body number was greater in infants compared with juveniles, and at the middle to posterior level of the arcuate nucleus, this developmental difference was statistically significant. Neurokinin B in the MBH exhibited a similar distribution to that of kisspeptin and was colocalized with kisspeptin in approximately 60% of kisspeptin perikarya at both developmental stages. Intensity of GnRH fiber staining in the median eminence was robust at both stages. These findings indicate that the switch that shuts off pulsatile GnRH release during infancy and that guarantees the subsequent quiescence of the prepubertal gonad involves a reduction in a stimulatory kisspeptin tone to the GnRH neuronal network.

Objectives Majoon-e-Seer Alvi Khan, a compound Unani formulation, has been indicated in disease conditions simulating dyslipidemia. The present study was done to substantiate the efficacy of Majoon-e-Seer Alvi Khan (MSAK) in dyslipidaemia on scientific parameters. Methods A randomized, single-blind, Standard controlled, clinical trial was carried out on 40 patients of dyslipidemia who were randomly allocated into test (n=30) and control (n=10) groups. The test drug, MSAK, and control drug, tablet Atorvastatin was given to the respective group for 60 days along with lifestyle modification. Results The test drug significantly alleviated the symptoms of subjective parameters (p<0.05). There was a statistically significant reduction in lipid profile of the patients in the test group (p<0.05) than control drug treatment. Conclusions The study evidenced that Majoon-e-Seer Alvi Khan is potentially effective and safe in the treatment of dyslipidemia. However, a multicentre study with a robust study design is required to generalize the results.

Objectives Majoon-e-Seer Alvi Khan, a compound Unani formulation, has been indicated in disease conditions simulating dyslipidemia. The present study was done to substantiate the efficacy of Majoon-e-Seer Alvi Khan (MSAK) in dyslipidaemia on scientific parameters. Methods A randomized, single-blind, Standard controlled, clinical trial was carried out on 40 patients of dyslipidemia who were randomly allocated into test (n=30) and control (n=10) groups. The test drug, MSAK, and control drug, tablet Atorvastatin was given to the respective group for 60 days along with lifestyle modification. Results The test drug significantly alleviated the symptoms of subjective parameters (p<0.05). There was a statistically significant reduction in lipid profile of the patients in the test group (p<0.05) than control drug treatment. Conclusions The study evidenced that Majoon-e-Seer Alvi Khan is potentially effective and safe in the treatment of dyslipidemia. However, a multicentre study with a robust study design is required to generalize the results.