Placental hypoxia, a major component of the pathophysiology of preeclampsia, is associated with various maternal vascular and endothelial dysfunctions. The higher incidence of preeclampsia at high altitude remains incompletely explained. The aim of the present study was to investigate the effect of high altitude on some endothelial and vascular dysfunction markers in normal and preeclamptic pregnancies. Eighty pregnant women (Paras 2-4) were enrolled in this study, which included four groups (each n = 20): normal pregnancies at low altitude (NL), normal pregnancies at high altitude (NH), preeclamptic pregnancies at low altitude (PL), and preeclamptic pregnancies at high altitude (PH). In normal pregnancies at high altitude serum ET-1, plasma TXA 2 , and serum TNF-α levels increased significantly with a significant reduction in plasma PGI 2 (66.81 ± 7.36, 122.86 ± 13.37, 102.23 ± 13.31, 191.57 ± 19.68, respectively) compared with the NL group (48.92 ± 4.58, 89.03 ± 10.67, 69.86 ± 7.97, 238.01 ± 24.55, respectively). In preeclampsia at low altitude serum ET-1, plasma TXA 2 , and serum TNF-α levels increased significantly with a significant reduction in plasma PGI 2 (88.39 ± 9.54, 162.73 ± 15.92, 142.39 ± 15.37, 149.155 ± 15.66, respectively) compared with both NL and NH groups. High altitude significantly augmented these changes in preeclamptic patients (117.75 ± 12.96, 211.01 ± 22.69, 196.86 ± 17.64, 111.92 ± 10.74) compared with PL, NH and NL groups. In conclusion hypoxia at high altitude aggravated the disturbances in the levels of ET-1, TXA 2 , PGI 2 and TNF-α associated with preeclampsia. This may contribute to the higher risk of preeclampsia at high altitude.

Pioglitazone (Pio) and swimming exercise (SE) are insulin sensitisers. This investigation was suggested because of the significant side effects associated with Pio treatment in metabolic syndrome (MetS). This study was, therefore, designed to investigate the preventive role of Pio treatment and SE in terms of efficiency and pathological changes in MetS in a rat model. Sixty male Sprague-Dawley rats were distributed equally among 6 groups: (i) control group (C), (ii) exercised control group (C+E), (iii) Pio-treated control group (C+Pio), (iv) group with MetS, (v) group with MetS treated with Pio (MetS+Pio), and (vi) exercised MetS group (MetS+E). Systolic blood pressure and heart rate were measured at the end of the experiments (16 weeks). Retro-orbital blood samples were used to determine the serum levels of glucose, insulin, lipids, gamma glutamyl transferase, alanine transaminase, aspartate transaminase, alkaline phosphatase, fetuin-A, and adiponectin. Semiquantitative reverse transcriptase - PCR insulin gene expression assays and hepatic histopathological examination were conducted. Swimming exercise significantly improved all of the aforementioned parameters, more so than the Pio treatment. In particular, the serum hepatic enzyme levels and hepatic histopathological changes were improved compared with the MetS group. These results suggested that swimming exercise might be an alternative physiological preventive tool against hepatic dysfunction to avoid the side effects associated with Pio treatment, and this could be demonstrated in a rat model of metabolic syndrome.

Pioglitazone (Pio) is a PPAR-γ agonist insulin sensitizer has anti-inflammatory activity. Our novel aspect was to investigate its hepatic anti-inflammatory activity at the level of ultra-structure and enzymatic changes in a high sucrose diet animal model. Forty male Sprague Dawley rats were divided into four equal groups: Control; control Pio; high sucrose diet; high sucrose diet Pio treated groups. Fourteen weeks later, serum glucose, insulin, lipogram, gamma glutamyle transferase, alanine transaminase, aspartate transaminase, alkaline phosphatase, fetuin-A and adiponectin levels were measured. Hepatic tissue homogenate levels of tumor necrosis factor-α, interleukin-6 and myeloperoxidase activity were determined. Microscopic and ultra-structure hepatic changes were conducted in all animal groups. Administration of Pio in HS+Pio group reduced significantly the hepatic inflammatory markers and the hepatic enzymes compared with HS group. Both light and electron microscopic examination revealed a great improvement of the hepatic tissue with Pio treatment. This study suggested that Pio treatment in obesity; in addition to insulin sensitizing activity; could protect the liver from the development of hepatic inflammation induced by a high sucrose diet not only at the enzymatic but also at ultra-structure levels.

Involvement of leptin in the pathogensis of preeclampsia (PE) is still a controversy subject. Several researches reported the changes in serum leptin in high altitude (HA) residents. The aim of the present work was to investigate the impact of oxidative stress (OS) induced by HA residence on maternal serum leptin in PE and if there was a significant correlation between the serum leptin with either OS or endothelial inflammatory markers. One hundred fifty eight pregnant women were included in this study, divided into: low altitude normal pregnancies (NL), HA normal pregnancies (NH), low altitude preeclamptic (PL), and HA preeclamptic (PH) who presented to the obstetrics and gynecology outpatient clinic in both Muhayl (500 m over sea level) and Abha General Hospitals (all of them resident at Alsoda district with the average altitude 2700 m over sea level). Serum leptin, superoxide dismutase (SOD) activity, malondialdehyde (MDA), plasma nitrite/nitrate (NOx), serum tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), blood urea nitrogen (BUN) and creatinine were determined. Both NH and PL groups showed significant increases in leptin (P< 0.01), SOD (P < 0.01), MDA (P< 0.001), NOx (P < 0.001), TNF-α (P < 0.001) and IL-6 (P < 0.001) compared with the NL group without any significant changes between both groups. The PH group showed significant accentuation of the previously measured parameters (P< 0.001 for all) compared with all other groups (NL, NH and PL groups). We can conclude that the combination of PE and HA residence resulted in significantly elevated maternal serum leptin suggesting involvement of leptin in the pathogenesis of PE accentuated by HA residence.