Safety of unoprostone isopropyl as mono- or adjunctive therapy in patients with primary open-angle glaucoma or ocular hypertension.

This review summarises the safety of unoprostone isopropyl (both at the 0.12 and 0.15% concentrations) instilled twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). For unoprostone 0.15%, combined data from two 12-month comparative monotherapy studies are reported, as well as data from three adjunctive therapy studies and two special population studies. With unoprostone monotherapy, most adverse events were mild or moderate and transient in nature. Less than 7% of unoprostone-treated patients discontinued therapy due to an adverse event. The most common adverse events associated with unoprostone were burning/stinging, burning/stinging directly upon drug instillation, ocular itching, and conjunctival hyperaemia. Unoprostone had no clinically notable effects on vital signs, laboratory profiles, or comprehensive ophthalmic examinations. One of 659 unoprostone 0.15%-treated patients had a change in iris colour after 12 months of monotherapy. Except for a higher incidence of burning/stinging and burning/stinging upon instillation, unoprostone was comparable to timolol 0.5% twice daily and betaxolol 0.5% twice daily. No safety concerns were raised with use of unoprostone as adjunctive therapy. Unoprostone had no significant effect on exercise-induced heart rate in healthy subjects or on pulmonary function in patients with mild-to-moderate asthma. The safety profile of unoprostone 0.15% was consistent with published information on the 0.12% formulation. In conclusion, unoprostone has an excellent safety profile in patients with POAG or OH.     

The role of alpha-adrenoceptors in the amnestic effect of intracerebroventricular dexamethasone.

Corticosteroids exert dual enhancing or impairing effects on cognitive functions. While their memory-enhancing effects have been well investigated, the mechanisms involved in their amnestic effects are not completely understood. Thus, we examined the role of alpha-adrenoceptors on dexamethasone-induced amnesia using step-through passive avoidance test in rat. Intracerebroventricular (i.c.v.) injection of dexamethasone (5 and 10 microg per rat) decreased the retention latencies. Likewise, intraperitoneal administration of alpha(2)-adrenoceptor agonist clonidine (0.1-0.3 mg kg(-1)) but not alpha(2)-adrenoceptor antagonist yohimbine (0.5-2 mg kg(-1)) decreased the retention latency. Yohimbine pre-treatment decreased the amnestic effects of dexamethasone or dexamethasone plus clonidine. On the other hand, intraperitoneal administration of alpha(1)-adrenoceptor agonist phenylephrine (0.5-2 mg kg(-1)) per se increased, while prazosin at 2 mg kg(-1) decreased the retention latency. Administration of phenylephrine before dexamethasone completely reversed the amnestic effect of the latter, while prozosin did not affect dexamethasone-induced amnesia. These data suggest that dexamethasone may induce its amnestic effect through activation of alpha(2)-adrenoceptors, leading to decreased alpha(1)-adrenergic activity.     

A dumbbell thrombus entrapped in patent foramen ovale

A 75-year-old lady came to emergency room due to dizziness andpresyncopal attacks during exertion since two days prior toadmission. Transesophageal echocardiography revealed a thrombuslike mass in right atrium traversing patent foramen ovale andextending to left atrium. Spiral chest CT scan showed bilateralpulmonary thromboemboli. Operative and pathological findingsconfirmed the diagnosis.     

Role of endogenous cannabinoids in ischemia/reperfusion injury following testicular torsion in rats

Objectives:   The role of endogenous cannabinoids in ischemia/reperfusion induced germ cell apoptosis in rats was investigated.
Methods:   Baseline group was for basal normal values. The Sham operated group served as a control group. The torsion/detorsion (T/D) group underwent torsion (1 h) and detorsion; AN1, AN2, and AN3 groups received anandamide (10 mg/kg) 30 min before torsion, 30 min after torsion, and just after detorsion, respectively. In the AM251 group, AM251 (0.5 mg/kg) was injected 45 min before torsion and in the AN/AM group, AM251 and anandamide were injected 45 and 30 min before torsion, respectively. Lipid peroxidation, antioxidant enzymes, and germ cell apoptosis was determined.
Results:   Malondialdehyde (MDA) levels in the T/D group were significantly higher than the control group. Moreover, MDA values in the AN1, AN2, and AN3 groups were significantly lower than T/D. There were significant decreases in catalase and superoxide dismutase activities in the T/D group versus the control group. These values in the AN1, AN2, and AN3 groups were significantly higher than T/D. It was also shown that MDA levels in the AN/AM group were significantly higher than the AN1 group. In the AN/AM group, catalase and superoxide dismutase activities were significantly lower versus the AN1 group. The mean germ cell apoptosis scores in all animals with testicular T/D were significantly higher than the control group. There was no difference between the apoptotic indices in the AN1, AN2, AN3, and T/D groups. Apoptosis scores in AM251 and AN/AM were significantly higher compared with the T/D and AN1 groups.
Conclusions:   Although anandamide increased antioxidant markers, it failed to reduce germ cell apoptosis. AM251 worsened the antioxidant defense system, which is reflected as higher germ cell apoptosis.     

The effect of oscillating-energy manual therapy on lateral epicondylitis: a randomized, placebo-control, double-blinded study.

Symptoms of lateral epicondylitis (LE) are attributed to degenerative changes and inflammatory reactions in the common extensor tendon induced by microscopic tears in the tissue after repetitive or overload functions of the wrist and hand extensor muscles. Conventional treatments, provided on the premise of inflammatory basis of LE, have shown 39-80% failure rate. An alternative approach suggests that symptoms of LE could be due to active tender points developed in the origin of hand and wrist extensor muscles after overuse or repetitive movements. Oscillating-energy Manual Therapy (OEMT), also known as V-spread, is a craniosacral manual technique that has been clinically used for treating tender points over the suture lines in the skull. Considering symptoms of LE may result from active tender points, the purpose of this study was to investigate the effect of OEMT on pain, grip strength, and functional abilities of subjects with chronic LE. Twenty-three subjects with chronic LE (>3mo) between ages of 24 and 72 years participated in this study. Before their participation, all subjects were screened to rule out cervical and other pathologies that could possibly contribute to their lateral elbow pain. Subjects who met the inclusion criteria were randomized into treatment and placebo treatment groups by a second (treating) therapist. Subjects were blinded to their group assignment. Subjects in the treatment group received OEMT for six sessions. During each treatment session, first a tender point was located through palpation. After proper hand placement, the therapist focused the direction of the oscillating energy on the localized tender point. Subjects in the placebo group underwent the same procedure, but the direction of the oscillating energy was directed to an area above or below the tender points, not covering the affected area. Jamar Dynamometer, Patient Specific Functional Scale (PSFS), and Numeric Rating Scale (NRS) were used to measure grip strength, functional status, and pain intensity and limited activity due to pain, respectively. The screening therapist who was blinded to the subjects' group assignment performed pretest, posttest, and six-month follow-up measurements. Subjects in the treatment group showed both clinically and statistically significant improvement in grip strength (p=0.03), pain intensity (p=0.006), function (p=0.003), and limited activity due to pain (p=0.025) compared with those in the placebo group. Follow-up data, collected after six months, showed no significant difference between posttest and follow-up measurements in functional activity (p=0.35), pain intensity (p=0.72), and activity limitation due to pain (p=0.34). Of all the subjects contacted for follow-up assessment, 91% maintained improved function and 73% remained pain free for at least six months. OEMT seems to be a viable, effective, and efficient alternative treatment for LE.     

Plasma estrogens, androgens, and von Willebrand factor in men on chronic hemodialysis

The role of sex hormones in atherogenesis has not been well defined. Since hemodialysis patients show signs of feminization and an increased propensity for atherosclerosis they are particularly suited to probe the relationship between estrogen, testosterone, and atherosclerosis. Therefore, we measured plasma total, free, and protein-bound estradiol (E2), testosterone (Te), and prolactin in 28 hemodialysis patients and in 30 age-matched controls. Von Willebrand factor (vWF) levels were also assayed. Total and free E2 as well as Te were significantly decreased in the patients (p less than 0.001). However, the E2/Te ratio was elevated in the patients (p = 0.05), as was vWF (p less than 0.01). No correlations were found between hormone levels and vWF, gynecomastia or vascular disease, but vWF and vascular disease were highly correlated. We conclude that in hemodialysis patients absolute estrogen levels are lower than normal, but that the estrogen/androgen ratio is shifted in favor of estrogen because of the coexistence of androgen deficiency. These findings suggest that an elevation in the estrogen/androgen ratio, rather than an increase in estrogen per se, may be a risk factor for atherosclerosis.     

A new synthetic approach for the preparation of polymer supports based on beaded copolymers of styrene and 2,4,5-trichlorophenyl acrylate: Synthesis and swelling behaviour of poly(styrene-co-acrylamide) resins

A new synthetic approach for the preparation of polymer supports/polymeric reagents is reported. The method is based on the chemistry of activated esters, and it is generally simpler than the methods conventionally employed for the preparation of funcationalized resins. Thus, the details of a series of beaded, and predominantly alternate, poly(styrene-co-2,4,5-trichlorophenyl acrylate)s is given. These activated resins were readily converted into highly functionalized poly(styrene-co-acrylamide) resins by aminolysis with a functional groups carrying amine. Resins with low degrees of functionality were obtained by partial aminolysis of the activated resins with a simples amine, and subsequent reaction with a functional group carrying nucleophile, or vice versa. A number of the new resins were examined for their swelling behaviour in a wide range of solvents and were found to show a considerably more general solvent compatibility than either styrene- or N,N-dimethylacrylamide-based resins. The relatively general solvent compatibility of the new resins is briefly discussed in terms of their copolymer structure and its is suggested that the dual “hydrophobic-hydrophilic”, character of these resins may be of important practical implications in, among others, solid phase peptide synthesis.