Time-Dependent Interaction of Ritonavir in Chronic Use: The Power Balance Between Inhibition and Induction of P-Glycoprotein and Cytochrome P450 3A

Ritonavir (RTV) is not only an inhibitor but also an immunoreactive inducer of both P-glycoprotein (Pgp) and cytochrome P450 (CYP) 3A in terms of its chronic use. The aim of present study was to test the hypothesis that the power balance between inhibition effects of RTV and induced activities of Pgp and CYP3A depends on the time after last RTV treatment (TimeR) in the chronic use of RTV; rhodamine 123 (Rho) and midazolam (MDZ) were administered at predetermined TimeR to rats pretreated with RTV for 7 days. After oral administration of Rho and MDZ to rats pretreated with RTV for 7 days, the areas under the plasma concentration-time curve of Rho and MDZ were significantly altered depending on TimeR: 1.27-, 0.79-, 0.95-, and 0.11-fold increases over that of the control for Rho at TimeR = 0, 3, 9, and 24 h and 3.12-, 1.50-, 1.27-, and 0.17-fold increases over that of the control for MDZ at TimeR = 0, 3, 9, and 24 h, respectively. These results revealed the presence of the time-dependent interaction of RTV with concomitant drugs in chronic use and should be taken into account in therapeutic strategies for HIV infection.     

Successful pregnancy after gonadotropin-releasing hormone analogue and hysteroscopic myomectomy in a woman with diffuse uterine leiomyomatosis

We report a patient with diffuse uterine leiomyomatosis, who wished to become pregnant. We performed hysteroscopic myomectomy after treatment with nafarelin acetate for 6 months. The patient conceived spontaneously soon after hysteroscopic myomectomy, and delivered a 2,798-g healthy baby.     

Does stress exacerbate liver diseases?

Although anecdotal comments on detrimental effects of psychosocial stress on liver diseases can be found even in the early literature, only recently has scientific evidence been reported. The present article reviewed such evidence to demonstrate how stress exacerbates liver diseases. A search of the literature from the last two decades was performed using MEDLINE by pairing ‘psychological stress’ with ‘liver’ or ‘hepatitis.’ Additional research was conducted by screening the bibliographies of articles retrieved in the MEDLINE search. The search results showed that the principal effectors of the activated hypothalamic–pituitary–adrenal (HPA) axis, glucocorticoids, can exert a facilitative effect on the hepatic inflammatory response and even increase the risk of developing hepatocellular carcinoma. For certain liver diseases, defective HPA axis activation, which probably contributed to the exacerbation of the liver disease, has been reported. The efferent sympathetic/adrenomedullary system mainly contributes to the stress‐induced exacerbation of liver diseases via its neurotransmitters, the catecholamines. In contrast, the efferent parasympathetic nervous system elicits an inhibitory effect on the development of hepatic inflammation. In conclusion, the pathophysiological interaction between stress and the liver appears to be regulated by the complex, dynamic networks of both the endocrine and autonomic nervous systems, which implies a further need for basic research into the involved mechanisms and for clinical evidence to apply psychosocial support to patients with chronic liver diseases.     

Protein-Losing Enteropathy in Systemic Lupus Erythematosus

Although protein-losing enteropathy can be associated with a variety of disorders, only three cases have been described in association with systemic lupus erythematosus. In the case described herein, protein-losing enteropathy was the only clinical manifestation of systemic lupus erythematosus. Small intestinal biopsy revealed edema and mild mononuclear cell infiltration in lamina propria mucosae and no evidence of lymphangiectasia. X-ray studies of the gastrointestinal tract were normal. Protein-losing enteropathy responded to high-dose corticosteroid therapy. Protein-losing enteropathy should be suspected as a possible cause of unexplained hypoalbuminemia in systemic lupus erythematosus.     

Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men

OBJECTIVE: To investigate the link between a reduction in blood pressure (BP) and daily exercise. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: 43 overweight Japanese men aged 32-59 years (BMI, 29.0+/-2.3 kg/m2) at baseline. Among the participants, a randomly selected 23 overweight men (BMI, 28.5+/-1.7) were further enrolled into the 10 months exercise program. MEASUREMENTS: BP was measured every week and steps per day were also recorded every day throughout the observation period. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical level, at before, 5 months and after intervention. Anthropometric parameters were also measured at same point. Aerobic exercise level, muscle strength, flexibility and calorie intake and insulin resistance (HOMA index) were investigated at before and after the study. RESULTS: In a cross sectional analysis, systolic BP (SBP) and diastolic BP (DBP) were significantly correlated with body composition. In a second longitudinal analysis, SBP was significantly reduced at 2 months and DBP was also reduced at 3 months, and almost maintained until the end of the observation period. Increasing daily walking was observed in 3 months and maintained until 10 months. Body composition, aerobic exercise level, muscle strength, flexibility and insulin resistance were significantly improved. There was positive correlation between DeltaDBP and Deltavisceral fat area (1-5, 5-10, 1-10 months). By stepwise multiple regression analysis, only Deltavisceral fat area was independently related to DeltaDBP at a significant level (1-10 months: DeltaDBP=-0.608+0.105Deltavisceral fat area, r2=0.227, P=0.0334). CONCLUSION: The present study indicated daily exercise lowers BP and visceral fat area is the critical factor for BP change.     

Permissive role of thyrotropin on thyroid radioiodine uptake during the recovery phase of subacute thyroiditis

Serial measurements of serum triiodothyronine (T₃), thyroxine (T₄), thyrotropin (TSH), and 4-hr thyroidal ¹³¹I uptake were carried out in nine patients with subacute thyroiditis. In the acute phase, suppressed TSH and ¹³¹I uptake were observed simultaneously with the elevations of T₃ and T₄. Thyrotropin-releasing hormone (TRH) failed to increase TSH in all patients studied. The mean value of an increment in serum TSH was only 1.8 μU/ml during the recovery phase when ¹³¹I uptake was normal or hyper-normal. In addition, and elevated ¹³¹I uptake was not necessarily associated with an immediate increase in the serum T₃ and T₄. These observations suggest that the resumption of the iodide pump may be more important than an increment in TSH in producing normal or hypernormal ¹³¹I uptake during the recovery phase. There appears to be a dissociation between the reestablishment of ¹³¹I uptake and the resumption of the mechanism of hormonal synthesis and secretion in the thyroid.     

Life‐threatening hemorrhage from the corona mortis after laparoscopic inguinal hernia repair: Report of a case

Along with the increased use of other laparoscopic procedures, laparoscopic inguinal hernia repair has become widely used because of its minimally invasive nature. Here, we report a case of 66‐year‐old man who underwent transabdominal preperitoneal laparoscopic hernioplasty and developed hemorrhagic shock on postoperative day 1. CT showed postoperative venous hemorrhage from the retropubic space. Successful hemostasis of the massive hemorrhage was achieved laparoscopically. The origin of the hemorrhage was assumed to be the corona mortis vein, which was slightly injured during the operation. Despite the rarity of this complication, surgeons must be aware of the need to carefully dissect and fix the mesh in the retropubic space to avoid injuring the corona mortis. Laparoscopic hemostasis may be an effective alternative to the open approach.