Nabil Bashir

Phospholipids regulate growth and function of MDCK cells in hormonally defined serum free medium

SummaryThe effects of the simple phospholipids phosphatidic acid (PA) and lysophosphatidic acid (LPA) on the growth and function of Madin Darby Canine Kidney (MDCK) cells has been studied. We observed that PA and LPA not only stimulated the growth of MDCK cells (at 20µM), but also stimulated the growth of normal rabbit kidney cells in serum free medium (albeit at a lower dosage of 5µM). Evidence was obtained that PA interacts synergistically with insulin so as to elicit a growth stimulatory effect. Recently, extracellular PA and LPA were proposed to stimulate mitogenesis in several types of animal cells by binding to particular sites on the plasma membrane which are coupled to signaling mechanisms such as adenylate cyclase via a pertussis toxin sensitive, inhibitory guanosine triphosphate binding protein (Gi protein) (15). However, even when the pertussis toxin dosage was increased to 50 ng/ml, LPA still had a dramatic growth stimulatory effect on MDCK cells. In the absence of LPA pertussis toxin was slightly growth stimulatory to MDCK cells. Phospholipids such as PA and LPA have been observed to prevent prostaglandin-induced increases in adenylate cyclase activity in other cell types via their effects on such a pertussis toxin sensitive Gi protein. If PA and LPA act on MDCK cells in this manner, then these phospholipids may possibly prevent the effect of PGE1 on the growth of normal MDCK cells. However PGE1 was still growth stimulatory to normal MDCK cells. The effects of PA on PGE1 independent variants of MDCK cells, which have elevated intracellular cyclic AMP levels (22), were also examined. In the presence of PA, PGE1 remained growth inhibitory, rather than growth stimulatory to the PGE1 independent cells. However, the PA dosage required to elicit an optimal growth response (5µM) was dramatically reduced, as compared with normal MDCK cells (20µM). This altered dosage requirement could be explained by the elevated intracellular cyclic AMP levels in the PGE1 independent variants. Like PGE1 and 8-bromocyclic AMP, PA and LPA also significantly increased the initial rate of Rb+ uptake by confluent monolayers of MDCK cells. The increase in the initial rate of Rb+ uptake could be explained by an increase in the ouabain-sensitive component of Rb+ uptake. An increase in the initial rate of ouabain-insensitive Rb+ uptake was also observed in LPA treated MDCK cell cultures.

Plasma levels of adrenocorticotropic hormone and cortisol in people living in an environment below sea level (Jordan Valley) during fasting in the month of Ramadan.

Objectives: To investigate the effects of Ramdan fasting on plasma levels of ACTH and cortisol in athletic students living in the Jordan Valley (JV) and compare them to those living at above sea level in Ramtha City (RC). Methods: Sample collection and measurements were done in November 1998 from non-fasting and in December 1998 from fasting people. Results: ACTH levels in non-fasting subjects in the JV were 36 ± 4 IU/ml compared to 43 ± 3 IU/ml for those in RC. Cortisol levels were 483 ± 76 (JV) and 539 ± 89 nmol/l (RC). Fasting led to an increase in ACTH (49 ± 6 (JV) and 58 ± 5 IU/ml (RC)) and cortisol levels (637 ± 101 (JV) and 805 ± 72 nmol/l (RC)). Conclusion: Fasting increases ACTH and cortisol levels in an altitude-independent fashion.

Serum zinc and copper levels in sickle cell anaemia and β-thalassaemia in North Jordan

Serum zinc and copper levels were determined in 28 beta-thalassaemia and 15 sickle cell anaemia (SCA) patients of 3-10 years of age using atomic absorption spectrophotometry. The results were compared with 25 age-matched controls. Copper levels were significantly increased in beta-thalassaemia and sickle cell anaemia. Zinc levels were significantly increased in beta-thalassaemia but significantly decreased in SCA. The data suggest the occurrence of impaired kidney function and disturbance in the metabolism of zinc and copper in these patients.

Prevalence of Hemoglobin S and β‐Thalassemia in Northern Jordan*

Objective: The aim of this study was to determine the incidence of HbS and β‐thalassemia in the Northern Jordan.

Seasonal Pattern Of Leutinizing, Follicle-Stimulating Hormone, Testosterone And Progesterone In Adult Population Of Both Sexes In The Jordan Valley

Differences were observed in hormonal levels between in both sexes of people living in Irbid City (620 meters above sea level) and in the Jordan Valley (360 meters below sea level. In addition, exercise was shown to differentially affect hormonal levels of both sexes at the above and below sea level locations. Serum levels of leutinizing hormone (LH) and testosterone (T) in adult male and serum levels of follicle-stimulating hormone (FSH) and progesterone (P) in adult female people were investigated in Irbid City and in the Jordan Valley during the years 1997 and 1998. The levels of these hormones were followed each month during this period. In males living in Irbid City, LH and T peaked from March through June, and in females at the same site, FSH and P also peaked from March through June. These data confirm the seasonal variation in sex hormones reported elsewhere in (wo) man and in other species. In males and females of the Jordan Valley, serum levels of LH, FSH, T and P were all higher than those of Irbid City throughout the year. Additionally, peaks of LH and T in male and FSH and P in female subjects in the Jordan Valley were observed from March through September. The high levels of these hormones and the extension of their peaks are suggested to be due to effects of the environmental factors of the Jordan Valley (high temperature, high barometric pressure) compared to those in Irbid City and other areas located at above sea level altitude.

Prevalence of haemoglobinopathies in school children in Jordan Valley.

Blood samples were drawn from 456 healthy children, 6-10 years old, to explore the prevalences of haemoglobinopathies in Northern Jordan Valley. The children were selected by the multi-stage random sampling technique. Complete blood count, haemoglobin electrophoresis and haemoglobin A2 (HbA2) estimations were carried out on all the samples. The prevalences of beta-thalassaemia minor, alpha-thalassaemia trait, sickle cell trait, and hereditary elliptocytosis were 15(3.3%), 16(3.5%), 2(0.44%) and 4(0.89%), respectively.

Thyroid Function in Children with β-Thalassemia Major in North Jordan

Basal thyroid function was assessed by serum thyroxine, tri-iodothyronine and thyroid-stimulating hormone levels in 90 patients 2-10 years old with beta-thalassaemia major. Based on measured serum ferritin levels, patients were classified into two groups: group (I) which included 63 patients with ferritin concentrations ranging from 300 to 7000 ng/ml (mild iron overload) and group (II) which included 27 patients with ferritin concentrations higher than 7000 ng/ml (severe iron overload). The results of thyroid function in both groups were compared with those of 50 control subjects. In group (I), the mean concentrations of all measured hormones were not significantly different from those of the controls. In group (II), the mean concentrations of thyroxine and tri-iodothyronine decreased by 29 and 35 per cent (P < 0.05), respectively, and the mean concentration of thyroid-stimulating hormone showed a 2.6-fold increase (P < 0.01) in comparison with those of the controls. The data clearly demonstrate the occurrence of impaired thyroid function and its possible association with iron overload in a considerable proportion of transfusion-dependent beta-thalassaemic patients.

Stress from exercise in the below sea level environment causes an increase in serum testosterone levels in trained athletes.

A comparative study (n = 20) of serum levels of leutinizing hormone (LH) and testosterone (T) between male trained athletes (high-shool students, 16–18 years old) living in North and South Shouna in the Jordan Valley (JV), 320–360 meters below sea level, and those living in Ramtha and Irbid, 550–650 meters above sea level, was conducted in November, 1999. Serum levels of LH and T were also measured in these athletes following a 20 Km non-competitive run. The air temperatures on the day of the experiment was comparable (25°C in North and South Shouna versus 23°C in Ramtha and Irbid). Before exercise, serum levels of LH and T in athletes of the below sea level environment (North and South Shouna) were similar to those levels in athletes of the above sea level environment (Ramtha and Irbid). Exercise caused a significant increase in serum levels of both LH and T only in athletes of North and South Shouna. It seems likely that the higher secretion of LH contributes, at least in part, for the higher serum levels of T following exercise. Taken together, these data suggest that exercise has an effect on LH and T secretion that is similar to that of fasting. And finally, the below sea level environmental factors, such as the high barometric pressure, as well as the genetic background of the athletes affect the pituitary and adrenal cortex as well as testicular tissue, resulting in the secretion of more LH and T.

Exercise at low altitude (Jordan Valley) causes changes in serum levels of acth, insulin, cortisol and lactate

This study was designed to examine the effects of exercise on adrenocorticotropic hormone (ACTH) and cortisol at low altitude (350 meters below sea level) and to compare these effects with those at a moderate level altitude (620 meters above sea level). Ten male trained athletes participated in a 21-K(m) non-competitive race. Serum levels of ACTH, luteinizing hormone (LH), growth hormone and cortisol were measured before and after the race at each of the altitudes. A significant increase in serum levels of ACTH was observed in response to this exercise only at low altitude. Serum levels of growth hormone were increased at both altitudes. Those of LH were not affected. Serum cortisol levels were increased following exercise at both altitudes. It is proposed here that ACTH may play a role in acclimatization to exercise at low altitudes. The role of growth hormone and LH in this conditioning process seems to be insignificant. Additionally, serum levels of insulin and lactate were also measured in these experiments. Exercise caused a decrease in serum insulin levels at both altitudes. Serum levels of lactate were decreased only at low altitude. These changes of serum levels of insulin and lactate suggest a type of metabolic adjustment to meet energy requirements. Changes in energy metabolism can be correlated by changes in the ratio of insulin to serum cortisol levels and those of other counter-regulatory hormones in response to exercise at both altitudes.

ACUTE EFFECTS OF EXERCISE AT LOW ALTITUDE (350 METERS BELOW SEA LEVEL) ON HORMONES OF THE ANTERIOR PITUITARY& CORTISOL IN ATHLETES

The purpose of this study was to examine the effects of exercise on anterior pituitary hormones (adrenocorticotropic hormone (ACTH), leutinizing hormone (LH) and growth hormone) as well as on cortisol at low altitude (350 meters below the sea level) and to compare these effects with those at a moderate level altitude (620 meters above the sea level). Ten male athletes with running experience participated in a 21-Km competitive race. Serum levels of ACTH, LH, growth hormone and cortisol were measured before and after the race at each of the altitudes. A significant increase in the serum levels of ACTH and growth hormone were observed in response to this exercise at low altitude. Similar exercise at 620 meters above the sea level resulted in a significant increase only in the serum levels of growth hormone. Serum levels of LH were not affected by this kind of exercise at both altitudes. Serum cortisol levels were increased following exercise at both altitudes. Altogether, these observations show a differential response of the anterior pituitary to exercise at low and normal altitudes. These data suggest that ACTH may have a role in the acclimatization to exercise at low altitudes. The role of growth hormone and LH in this conditioning process seems to be insignificant. The changes in serum cortisol levels in response to exercise at both altitudes correlate well with the effect of exercise on energy metabolism.