Ramani Varghese

Kuwait University, Kuwait, Muhafazat al `Asimah, Kuwait

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Publications (4)7.34 Total impact

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    ABSTRACT: Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls. Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.
    International Journal of Urology 04/2006; 13(4):354-61. · 1.73 Impact Factor
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    ABSTRACT: To investigate the morphological effects of free radical injury on spermatogenic cells in both testes of the rabbit experimental model of testicular torsion. The left testes of 8 peripubertal NZW rabbits (3-6 months) were subjected to 0, 15, 30, 60, 90, 120, and 180 min of ischemia by applying a clamp to the spermatic cord, followed by reperfusion. Another set of 8 rabbits was subjected to 60 min of ischemia and administered antioxidants (acetylsalicylic acid, ascorbic acid, allopurinol, quercetin, superoxide dismutase) before reperfusion. Both testes of 4 animals per group were harvested at 24 h and the remaining 4 at 3 months. Johnsen scores for spermatogenic activity and other changes were assessed histologically and these were compared with testicular malondialdehyde (MDA), a measure of free radical damage, assayed on testicular homogenates using the thiobarbiturate method. In the 24-hour reperfusion group, apoptotic bodies and giant cells were more prominent in the seminiferous tubules of the left testes compared to the right, and were maximal after 90 min. In the 3-month reperfusion group, giant cells were absent, and apoptotic bodies were reduced in both testes. Testicular MDA showed an increase only in the left testes in the 24-hour reperfusion group, while the 3-month group showed increased MDA levels in both testes, but more on the left. The Johnsen score fell only to 8.0 in the left testes in the 24-hour reperfusion group, but dropped to 2.3 in the 3-month reperfusion group. Only in the 3-month reperfusion group, did antioxidant-treated animals show a fall in Johnsen scores in the left testes, regardless of the type of antioxidant. These findings confirm a role for reactive oxygen species (ROS) in damage to spermatogenic cells in both the ipsilateral and contralateral testes following torsion, with longer term effects in the torted testis. Currently available antioxidants do not provide any significant long-term protection against morphological damage to the testis by ROS generated in testicular torsion.
    Urologia Internationalis 02/2005; 75(3):258-63. · 1.07 Impact Factor
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    ABSTRACT: Experimental studies of the use of free radical scavengers in ischemic/reperfusion (I/R) injury following detorsion of the torted testis have yielded conflicting results due to differences in the period of ischemia used. The authors studied I/R injury in the rabbit model, to define the point beyond which there is reperfusion failure. Ischemia/reperfusion injury of the testis was created in 3-6-month-old male New Zealand white rabbits by cross-clamping the left spermatic cord for periods of ischemia lasting 0, 15, 30, 60, 90, 120 and 180 min. There were eight animals per experimental group. The right testis served as internal control. Both testes were harvested after 24 h of reperfusion in four animals and after 3 months in the remaining four animals for each group. Testicular malondialdehyde (MDA), a measure of free radical damage, was determined by using the thiobarbituric acid reaction on testicular homogenates. Johnsen score was used to assess morphological damage caused by the ischemia. After 24 h of reperfusion, the mean testicular MDA in the control right testes at 0, 15, 30, 60, 90, 120 and 180 min was 2.1, 2.5, 2.9, 2.4, 2.1 and 1.9 nmol/mg protein, respectively. The mean left testicular MDA at corresponding ischemic periods was 1.6, 2.0, 3.9, 10.0, 4.4, 6.1 and 1.0 nmol/mg protein, respectively. The maximum left testicular MDA was at 60 min (10.0 nmol/mg protein), following which the level dropped significantly to 1.0 nmol/mg protein at 180 min. At 3 months, the mean Johnsen scores for left testes subjected to 0, 60, 120 and 180 min ischemia were 9.4, 8.8, 2.3, 3.5, respectively. The results suggest that following ischemia of up to 60 min in the rabbit testis, adequate reperfusion is possible, but ischemia lasting beyond 60 min results in inadequate reperfusion leading to irreversible damage. Thus, in experiments for assessing the effect of antioxidants on I/R injury of the testis in rabbits, periods up to 60 min of ischemia should be regarded as optimum to observe an effect.
    International Journal of Urology 02/2005; 12(1):81-9. · 1.73 Impact Factor
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    ABSTRACT: The incidence of clinical prostate cancer in the Arab population is among the lowest in the world. High serum IGF-1 level has been implicated as a possible risk factor for the development of prostate cancer in Caucasians. The purpose of this study was to determine serum IGF-1 and IGFBP-3 levels in healthy Arab men and in Arab men with newly diagnosed benign prostatic hyperplasia (BPH) and prostate cancer, and to compare these values with values reported in Caucasians. Subjects were recruited in two groups: (a) indigenous, healthy Arab men aged 15-90 y (n = 383); (b) Arab men with newly diagnosed prostate cancer (n = 30) or BPH (n = 40). Blood was obtained from fasting patients and volunteers, between 8:00 a.m. and 12:00 noon. The serum concentrations of IGF-1 and IGFBP-3 were determined using Immunoradiometric assay (IRMA) kits. As in Caucasians, serum IGF-1 and IGFBP-3 levels declined with age in Arab men. The mean +/- s.d. of serum IGF-1 levels in healthy Arab men in the age group 15-20, 51-60, 61-70 y were lower (376.2 +/- 153.2, 134.9 +/- 105.7 and 89.6 +/- 48.4 ng/ml, respectively), compared to values reported for similarly aged Caucasians. Arab men with newly diagnosed prostate cancer had significantly higher serum IGF-1 level (P < 0.01) and lower IGFBP-3 levels (P < 0.01) compared to age-matched Arabs without the disease. Arab men have lower serum IGF-1 levels compared to Caucasians and this may be an important factor in the explanation of the low incidence of prostate cancer in the Arab population.
    Prostate Cancer and Prostatic Diseases 01/2005; 8(1):84-90. · 2.81 Impact Factor