M. T. Abdel Aziz

Clinical, biochemical, and experimental studies on lactation

Abstract The effect of administration of various contraceptive tablets, namely, Lyndiol 2.5, Lyndiol 1.0, and lynestrenol 0.5 mg., and Deladroxate injection on milk composition was investigated. A diminution was observed in milk proteins and milk fat which was statistically significant in all cases, compared to a control (placebo) group. Narrow variations were observed in milk lactose which were, however, statistically insignificant. The milk inorganic constituents, namely, sodium, potassium, calcium, and magnesium, were significantly decreased. The total inorganic phosphorus showed no change except in the lynestrenol 0.5 mg. and Deladroxate groups, in which it was diminished. The above findings speak strongly in favor of an adverse effect of these steroids on milk composition. The possible role played by these drugs in this concern is discussed.

Effect of mesenchymal stem cell penile transplantation on erectile signaling of aged rats

Stem cell‐based therapy targeted at the penile tissue has been lately considered in preclinical studies. This work aimed to assess the effect of intracavernous administration of mesenchymal stem cells (MSCs) in aged rats (n = 100). They were subjected to single intracavernous injection (ICI) of 1.0 million MSCs, followed up for 3, 4 weeks, 3 and 4 months (each group 25 rats) and compared with both adult and aged controls (n = 50). In dissected cavernous tissues, cGMP and histopathology were assessed in addition to intracavernous pressure (ICP) measurement in some anaesthetised rats. The results showed that cavernous tissue cGMP was significantly increased in MSCs transplanted rats in all investigated groups compared with the controls. The mean cavernous cGMP levels after 3 and 4 months of MSCs transplantation were significantly increased compared with those after 3 or 4 weeks. Cavernous tissue ICP measurement showed significant increase in MSCs transplanted groups compared with the controls, more in the long‐term follow up than in the shorter one. Histopathological examination detected markedly dilated sinusoidal vascular spaces in the long‐term follow‐up study. It is concluded that stem cell‐based therapy is feasible for age‐associated erectile dysfunction and could improve erectile signaling.

Heme oxygenase enzyme activity in seminal plasma of oligoasthenoteratozoospermic males with varicocele.

This work aimed to assess seminal plasma heme oxygenase (HO) enzyme activity in oligoasthenoteratozoospermia (OAT) males with varicocele. Ninety‐three men were divided according to their sperm count and clinical examination into: healthy fertile controls (n = 34), OAT without varicocele (n = 37) and OAT associated with varicocele (n = 22). They were subjected to semen analysis and estimation of seminal plasma HO enzyme activity in the form of bilirubin concentration. Seminal plasma HO enzyme activity decreased significantly in OAT cases compared with controls. Seminal plasma HO in OAT cases associated with varicocele decreased significantly compared with OAT cases without varicocele and healthy controls (mean ± SD; 109.2 ± 29.5, 283.6 ± 88.4, 669.5 ± 236.1 nMol bilirubin/mg ptn/min, P < 0.001). There was positive correlation between seminal plasma HO enzyme activity and sperm concentration, per cent of motile spermatozoa, number of motile spermatozoas ml−1 and significant negative correlation with sperm abnormal forms per cent. It is concluded that varicocele has a negative impact on seminal HO enzyme activity. Therefore, improved seminal picture after correcting varicocele repair might be related, in part, to improved HO action(s).

Oral phosphodiesterase-5 inhibitors: effect of heme oxygenase inhibition on cGMP signalling in rat cavernous tissue.

This work postulated that heme oxygenase (HO) is partly responsible for controlling phosphodiesterase‐5 inhibitor actions by modulating cyclic guanosine monophosphate (cGMP) cavernous tissue levels. Five hundred and four male Sprague–Dawley rats, divided into five groups, were investigated. Group 1 (n = 72) included controls, group 2 (n = 72) received sildenafil citrate (ViagraR) orally, group 3 (n = 72) received vardenafil hydrochloride (LevitraR), group 4 (n = 72) received tadalafil (CialisR). Group 5 (n = 216), subdivided into three subgroups (A, B and C, 72 each), received the same dose of each drug with the HO inhibitor, Zn protoporphyrin. Eight rats from each group/subgroup were killed at 0.5, 1, 2, 3, 4, 6, 18, 24 and 36 h when cGMP levels in the cavernous tissues were estimated. Cavernous tissue cGMP levels increased significantly in sildenafil, vardenafil and tadalafil‐treated rats compared to the controls with significant decreases after HO inhibition. It is concluded that the effects of these PDE‐5 inhibitors in rat cavernous tissue are partly mediated through HO activity via the cGMP signalling pathway.

Effect of HO-1 cDNA-liposome complex transfer on erectile signalling of aged rats.

This work aimed to assess the efficacy of haeme oxygenase‐1 (HO‐1) cDNA‐liposome complex transfer as a mediator of erectile signalling in aged rats. One hundred and fifty aged white albino rats were equally divided into five groups: controls, rats receiving lipofectamine, rats receiving intracorporeal HO‐1 cDNA‐lipsome complex, rats receiving HO‐1 cDNA‐liposome complex plus nitric oxide synthase (NOS) inhibitor, and rats receiving HO‐1 cDNA‐liposome complex plus HO inhibitor. Six rats were killed from each group after 12, 24 and 48 h, and after1 and 2 weeks. In dissected cavernous tissues, the following were assessed: HO‐1 gene expression, Western blot for HO‐1, HO enzyme activity, cGMP and histopathology. The results showed that HO‐1 cDNA‐liposome complex transfer led to a significant increase in cavernous tissue HO‐1 protein, HO‐1 gene expression, HO enzyme activity and cGMP up to 1 week. NOS inhibition exhibited no effect on HO‐1 gene enhancement of cavernous tissue HO enzyme activity or cGMP, whereas inhibition of HO significantly decreased these parameters. Histopathology of cavernous tissue demonstrated a significant dilatation of helicine arteries in HO‐1 cDNA‐liposome complex treated group after 48 h compared with the controls. It is concluded that HO‐1 cDNA‐liposome complex transfer augments cavernous tissue cGMP with subsequent sinusoidal relaxation.

Seminal Lipids as Energy Substrate for the Spermatozoa

Seminal‐Lipide als Energie‐Substrate für die Spermatozoen

Heme oxygenase enzyme activity in human seminal plasma of fertile and infertile males.

This work aimed to assess heme oxygenase (HO) enzyme activity relationship with different human semen parameters. One hundred and twenty men were divided according to their sperm count and clinical examination into: obstructive azoospermia (n = 20), nonobstructive azoospermia (NOA) (n = 25), oligozoospermia (n = 35) and normozoospermia (n = 40). Semen analysis, western blot for HO‐1 and HO‐2, and estimation of seminal plasma HO enzyme activity chemically in the form of bilirubin concentration were carried out. Seminal plasma HO enzyme activity was very low in OA specimens, low in NOA, moderate in oligozoospermia while higher in normozoospermia (mean ± SD; 6.26 ± 2.2, 81.4 ± 35.5, 283.8 ± 90.1, 657.4 ± 227.6 pmol ml−1 min−1) with significant differences. Western blot analysis demonstrated HO‐2 expression in all studied groups whereas HO‐1 was highly expressed in fertile normozoospermic group compared with other groups. There was positive correlation between seminal plasma HO enzyme activity and sperm concentration, sperm motility percentage, motile spermatozoa ml−1 and sperm normal morphology per cent. It is concluded that HO enzyme activity in the human seminal plasma is related to spermatogenesis and sperm‐motility processes.

Clinical biochemical, and experimental studies on lactation. IV. Quantitative and qualitative changes induced in goat's milk by gestagens.

Abstract A study was planned on the effect of contraceptive steroids on milk yield and composition in goats after established lactation. The goats were classified into six groups: Group I received no medication and was considered as a control group. Group II was given Deladroxate injections. Groups III and IV received Lyndiol 2.5 and Lyndiol 1.0, respectively. Group V received lynestrenol 0.5 mg. alone and Group VI, mestranol 0.1 mg. alone. The milk yield per 24 hours was found to decrease in all groups, the drop amounting to 42 per cent in the control group, 71.6 per cent in Group II, 60 per cent in Group III, 52 per cent in Group IV, 55.6 per cent in Group V, and 56 per cent in Group VI. The growth rate of the kids in Groups II, III, and IV was lower than that in the control group. The milk fat and proteins dropped gradually. This was most marked in medicated groups. Milk lactose showed minor variations, while the changes in the inorganic constitutents were inconsistent, varying between increment and decrement. These results confirm the previous findings in women, that gestagens exert an adverse effect on the quantity and quality of milk when they are orally or parenterally administered during lactation.

Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κβ and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κβ, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κβ, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction.

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐Ҡβ, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐Ҡβ, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.