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Biomedical subjects

M Khalid

Publications and source records attributed to M Khalid.

33 records · Page 2Linked to original sources

Growth hormone priming as an adjunct treatment in superovulatory protocols in the ewe alters follicle development but has no effect on ovulation rate.

This study investigated the effect of FSH alone and rGH priming followed by FSH treatment on follicle populations, follicular fluid concentrations of components of the IGF system and steroids, and the ovulation rate in sheep. Estrus was synchronized with progestagen sponges. Ewes (n = 10/group) in Group 1 served as untreated controls, while those in Groups 2 to 5 received a standard superovulatory treatment of 1.1 mg i.m. oFSH twice daily for 4 d. In addition, ewes in Groups 3 and 5 were administered rGH (15 mg/d, i.m.) for the 7 d prior to FSH treatment. Groups 1, 2 and 3 were sacrificed just prior to the LH surge; Groups 4 and 5 were allowed to ovulate. Daily plasma samples were collected to monitor GH, IGF-1 and insulin levels. All follicles > or = 1.0 mm from Groups 1, 2 and 3 were counted, and follicular fluid from follicles > or = 2.5 mm was assayed for estradiol, testosterone, IGF-1 and IGFBPs. Compared with the control, treatment with rGH + FSH but not FSH alone increased (P < 0.001) plasma concentrations of GH, IGF-1 and insulin. The mean number of large-(> or = 4.5 mm) and medium-sized (2.5 to 4.0 mm) follicles was increased (P < 0.01), and the mean number of small (< or = 2.0 mm) follicles was decreased (P < 0.001) by FSH treatment. The mean number of medium-sized (2.5 to 4.0 mm) follicles was further increased (P < 0.05) by rGH priming. Estradiol concentration in medium but not in large estrogenic follicles was increased (P < 0.05) by rGH priming, whereas testosterone concentration in estrogenic follicles was not altered. Components of the IGF system in medium-sized estrogenic follicles were similar in all treatment groups; however, in large estrogenic follicles rGH increased IGF-1 concentrations (P < 0.05) and intensity of the 44-42 kDa IGFBP band (P < 0.01). Priming with rGH did not alter superovulatory responses. These results show that rGH priming, when used as an adjunct to FSH treatment in ewes, alters components of the IGF system in large estrogenic follicles and increases the number and physiological maturity of medium-sized follicles in the ovary; it does not however alter ovulation rate responses.

Animals↗

Cutaneous leishmaniasis in Multan, Pakistan.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in certain areas of Pakistan. This study was carried out to determine the incidence and clinical pattern of the disease in Pakistan. METHODS: CL patients presenting in the out-patient clinic of the Department of Dermatology, Nishtar Hospital, Multan from January 1995 to June 1997 were included in the study. The patients were diagnosed clinically and confirmed by laboratory demonstration of the parasite in a Giemsa-stained smear from the lesion. All important clinical details were recorded on specially designed forms. RESULTS: Three hundred and five patients with 681 lesions were seen during 30 months. All the lesions were of the dry type. Most of the lesions (97%) were present on exposed areas of the body. One hundred and thirty-four (44%) patients had one and 75 (24%) had two lesions. Eight five per cent of the sufferers were less than 30 years of age. The disease was slightly more preponderant in males (60%). Most cases presented during winter. CONCLUSIONS: Lack of wet type lesions may be due to complete absence of Leishmania major in this area. This is in contrast to other areas of Pakistan where both dry and wet types of CL are present.

Adolescent↗

Effect of progesterone pre-treatment on steroid secretion rates and follicular fluid insulin-like growth factor-1 concentrations in seasonally anoestrous ewes treated with gonadotrophin releasing hormone.

Progesterone priming is known to prevent premature luteal regression in seasonally anoestrous ewes induced to ovulate with small dose multiple injections of gonadotrophin releasing hormone (GnRH), but the precise mechanisms involved are poorly understood. The main objective of the present study was to investigate the effect of progesterone priming, before and after a period of treatment with GnRH, on the biochemical activity of ovarian follicles collected from seasonally anoestrous ewes. Ewes in Groups 1 and 2 (6 ewes/group) received progesterone priming or vehicle alone, respectively, and were slaughtered 72 h later. Ewes in Groups 3 and 4 (6 ewes/group) were similarly primed with progesterone or vehicle only, respectively, and then 72 h later received 2-hourly injections of 250 ng GnRH for 20 h, followed 2 h later by a single bolus injection of 300 micrograms GnRH. They were then slaughtered 2 h after the bolus injection. All normal growing follicles > or = 2.0 mm diameter were dissected from the ovaries of all ewes and after measurement of their diameter, were incubated in Eagle's Basal Medium for 2 h to measure their steroid secretion rates. The fluid from each follicle was then aspirated and assayed for total insulin-like growth factor-1 (IGF-1) content. The luteinizing hormone receptor content of the whole follicle was estimated using 125I-labelled human chorionic gonadotropin (hCG). The follicles were classified as either non-oestrogenic or oestrogenic if their oestrogen production rate was < or = 300 or > 300 pg/ml/2h, respectively. The mean diameter of oestrogenic follicles (5.72 +/- 0.25 mm) was significantly (P < 0.001) larger than that of non-oestrogenic ones (3.93 +/- 0.25 mm). The mean numbers of oestrogenic and non-oestrogenic follicles were not significantly different among the four treatment groups. Oestradiol production rate was significantly (P < 0.001) increased as a result of GnRH treatment, but only in large oestrogenic follicles. Testosterone production rate was, however, significantly (P < 0.05) increased by both GnRH and progesterone in both classes of follicle. While GnRH treatment tended to decrease IGF-1 concentrations in small non-oestrogenic follicles, it significantly (P < 0.05) increased concentrations in large oestrogenic ones. IGF-1 concentrations were, however, significantly (P < 0.05) increased in both classes of follicle collected from progesterone-primed ewes treated with GnRH. Regardless of treatment, follicular fluid IGF-1 concentrations were significantly (P < 0.001) higher in small non-oestrogenic follicles compared to large oestrogenic ones. An increase in 125I-hCG binding to large oestrogenic follicles was observed in response to progesterone (P-0.07) in GnRH treated ewes. These results indicate differences in the biochemical activity of follicles attributable to progesterone priming which may be casually related to defective luteal function after ovulation.

Anestrus↗

Calcium efflux from an intracellular pool activated by GTP hydrolysis in cultured gastric smooth muscle.

In these studies, we have characterized calcium movement due to guanosine triphosphate (GTP) hydrolysis from an ATP-sequestered intracellular calcium pool in cultured gastric smooth muscle. GTP (1-100 microM), when added to an ATP-regenerating medium, resulted in a concentration-dependent and irreversible efflux of calcium from an organellar calcium pool. GTP-induced calcium efflux was not affected by variation of the ATP/ADP ratio (8.5-155.0), indicating that GTP did not act by inhibiting calcium influx via calcium adenosinetriphosphatase. To assess whether the calcium increase was necessarily associated with GTP hydrolysis, experiments were performed with the nonhydrolyzable guanine nucleotide analogues guanosine 5'-[beta-thio]diphosphate (GDP beta S), 5'-guanylyl imidodiphosphate guanosine (GppNHp), and 5'-O-(3-thiotriphosphate) (GTP gamma S). Administration of GDP beta S and GppNHp resulted in no significant calcium efflux. GTP gamma S caused a small steady-state calcium increase (20% of that induced by the hydrolyzable nucleotide) but irreversibly inhibited all subsequent calcium increase due to GTP. The possibility that GTP may either modify the concentration of mobilizable calcium in inositol trisphosphate (IP3)-sensitive calcium stores or the responsivity of IP3-associated calcium channels was assessed by two experiments: 1) prior administration of GTP at concentrations < or = 100 microM had no effect on IP3-induced calcium release, and 2) heparin, which competitively inhibits IP3 binding to its receptor on the endoplasmic reticulum, did not affect GTP-associated calcium increase. These results demonstrate that, in gastric smooth muscle, GTP causes calcium efflux from an intracellular pool that is functionally independent from that pool sensitive to IP3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

[Abandonment, therapeutic relentlessness or euthanasia].

Which standards and values should guide our conduct relating to death and palliative care? Who, in the end, has the right to decide whether or not to administer a life extending therapy to terminally-ill patients? Where exactly is the border between an ordinary treatment and an extraordinary or a relentless one? Should euthanasia be legalized or not? These are some of the basic questions caregivers and health professionals who work with the dying are now asking themselves. To delve deeper into these questions and help to find the answers, the author draws a collective typology of the main ideas people have on these problems. The differences between the various trends of thinking regarding death are explained. The author concludes with a plea in favor of the principle where the dying patient becomes the centre of the end of life and agony process. Therefore, it is the caregiver's responsibility to grant the patient the right to be informed, to ask for or refuse therapeutic relentlessness, or to die with dignity and serenity.

Euthanasia↗

N-methyl-D, L-aspartate induces a transient increase in LH secretion in the seasonally anestrous ewe.

The primary objective of this study was to determine the LH response to an excitatory amino acid agonist, N-methyl-D, L-aspartate (NMA) in the seasonally anestrous ewe. In experiment 1, 3 i.v. injections of NMA were given; doses of 0.5, 1.5 and 4.5 mg/kg BW were tested. LH response to NMA depended on the dose. There was little response to the lowest dose. All animals responded to the first injection of the intermediate and the highest doses (mean pulse amplitude: 9.2 +/- 0.4 and 6.8 +/- 1.2 ng ml, respectively). The responses to the second or third injections of both doses were variable and were either absent or reduced compared to that of the first. In experiments 2 and 3, ewes were given 3 injections of normal saline (NS) followed by 3 injections of NMA (1.25 and 4.5 mg/kg BW, respectively) at 2 hr intervals. The last injection of NMA was followed 2 hr later by an injection of GnRH (3.0 ng/kg BW). In experiment 2, the first NMA injection induced an immediate LH pulse (mean pulse amplitude: 8.0 +/- 1.6 ng/ml) in all ewes, however, the second and third injections induced LH pulses in only 25% and 75% (mean pulse amplitude: 2.2 and 2.4 +/- 0.6 ng/ml) of the ewes, respectively. In experiment 3, NMA increased mean LH release (P less than 0.05) after all injections, but responsiveness to the third injection was reduced in some ewes. GnRH injections induced LH release in all ewes in experiments 2 and 3 (mean pulse amplitude: 6.9 +/- 1.8 and 6.4 +/- 2.2 ng/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗

Pulsatile GnRH administration stimulates the number of pituitary GnRH receptors in seasonally anoestrous ewes.

Twenty seasonally anoestrous ewes were pretreated with progesterone for 4 days and divided into four equal groups. Ewes in Group 1 received no GnRH treatment and were slaughtered immediately after progesterone removal. Ewes in Groups 2, 3 and 4 received i.v. injections of 250 ng GnRH every 2 h for 36 h starting at the time of progesterone removal. Ewes in Group 2 were slaughtered immediately after the 36 h GnRH pulsing, while ewes in Groups 3 and 4 were given a bolus injection of 125 micrograms GnRH at this time and were slaughtered 2 and 10 h after the bolus injection, respectively. Blood samples were collected every 30 min from ewes in Group 4 only, from 4 h before the start of GnRH treatment until 10 h after the bolus injection. Pulsing with GnRH resulted in episodic release of LH, and the bolus injection of GnRH was immediately followed by a preovulatory type LH surge in those ewes in which an endogenous surge had no already begun. The pituitary GnRH receptor numbers were significantly higher for the ewes in Group 2 than for any of the other treatment groups, while there was no significant difference in the receptor numbers between Groups 1, 3 and 4. The results suggest an up-regulation of GnRH receptors resulting from pulsatile GnRH therapy.

Anestrus↗

N,N'-disubstituted L-isoglutamines as novel cancer chemotherapeutic agents.

Previous studies carried out in the authors' Institute revealed that one of the active metabolites of Antineoplaston A10 is phenylacetylisoglutamine. The objective of this study is screening of N,N'-disubstituted L-isoglutamine derivatives for selection of novel anticancer agents. A series of seven derivatives of L-isoglutamine was synthesized as potential chemotherapeutic agents. Antitumor activity studies were performed in tissue culture of breast carcinoma cells HBL-100. The acute toxicity study was carried out on a group of 60 HA/ICR Swiss mice. Among the compounds tested N alpha-(phenylacetylamino)-gamma-(4-amino-N-benzyl-piperidinyl)-L-g lutamyl amide was found to have the best anticancer activity and no significant acute toxicity. The LD50 was calculated by the moving average method and determined as 4.5 g/kg i.p. in mice. It is concluded that the important structural features for good antineoplastic activity are lipophilic groups on both amine and amide nitrogen of isoglutamine. The activity is also increased when the phenyl group present at the side chain is at least two carbon atoms away from the amide nitrogen.

Animals↗

Post-traumatic subdural hygromas: observations concerning a surgical enigma.

Four per cent (38) of 881 head injured patients developed known subdural hygromas. Their times of onset and course were variable. However, only two large hygromas seemed clinically significant. Hygromas were more frequent when intracranial pressure monitors were placed, possibly due to opening of the arachnoid, particularly if intracranial pressure was low. But, of course, monitors were only inserted in more severely injured patients. The use of Richmond bolts to drain subdural hygromas in a controlled fashion while monitoring intracranial pressure is suggested.

Adult↗

Anthropometric comparison between high- and low-altitude Saudi Arabians.

Measurements of weight, height, mid-upper arm circumference, mid-upper arm muscle circumference and skinfold thickness over the triceps region were made in 437 high-altitude residents (3150m above sea level) aged 16-60 years and 468 low-altitude residents (500 m above sea level) aged 16-60 years in southern Saudi Arabia. Compared with low-altitude residents, high-altitude residents were found to be significantly heavier and taller, but to have nearly similar mid-upper arm circumference, mid-upper arm muscle circumference and triceps skinfold thickness. Estimates of body fat have been made from the triceps skinfold measurements. No significant difference in the percentage of fat was detected between high- and low-altitude residents. When fat mass (kg) and fat mass index (fat mass (kg)/height in m2) were considered, similar trends were found between highland and lowland men only. Highland women showed significantly higher fat mass and fat mass index when compared with lowland women. These differences in physique between highland and lowland residents of southern Saudi Arabia may be attributed to the effect of environmental factors, possibly the hot climate and parasitic infections prevalent in lowland areas, in addition to the higher physical activity observed in lowland women.

Adolescent↗