Do effects of propranolol on the skeletal system depend on the estrogen status?

BackgroundPropranolol, a nonselective β-adrenergic receptor antagonist, was reported to favorably affect the skeletal system in different animal models. The aim of the study was to investigate whether the effects of propranolol on the skeletal system depend on the estrogen status.MethodsThe in vivo experiments were carried out on the following groups of mature female Wistar rats: sham-operated control rats, sham-operated rats receiving propranolol, ovariectomized (OVX) control rats, OVX rats receiving propranolol, OVX rats receiving estradiol, OVX rats receiving estradiol and propranolol. Propranolol hydrochloride (10 mg/kg po) and/or estradiol (0.1 mg/kg po) were administered daily for 4 weeks. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, and mechanical properties were examined. In vitro, effects of estradiol and propranolol on the formation of mouse osteoclasts and on the mRNAexpression of genes related to osteoclastogenesis, bone formation and mineralization, as well as adrenergic and estrogen signalling in mouse osteoblasts were investigated.Results and conclusionPropranolol exerted some favorable effects on the rat skeletal system in vivo, independently of the estrogen status. However, in vitro studies indicated a possibility of some antagonistic relations between the estradiol and propranolol effects.     

Zinc as a marker of affective disorders

Depression is considered as a chronic and recurring illness with functional impairment, significant disability, morbidity and mortality. Despite the extensive research carried out on depression, its pathophysiology is still poorly understood. An important problem concerning research into depressive disorder is the lack of biological markers which could improve diagnosis or indicate a risk of developing depression or risk of relapse. Several reports indicated decreased zinc concentrations and even its deficit in clinical depression, so the measurement of the concentration of this element in the blood of patients was suggested as a useful and specific clinical marker of depression. The reported results indicated that the serum zinc level might be a marker of depression as a state (state marker) in treatment responsive patients. However, in drug-resistant depression a decreased concentration of zinc may be a marker of traits (trait marker). It seems, however, that the measurement of the concentrations of zinc might be in the future a component of the battery of tests; of markers of immune activation and oxidative stress rather than itself alone.     

Cytochrome P450 3A and their regulation

CYP3A isozymes collectively comprise the largest portion of the liver and small intestinal CYP protein and they are involved in the metabolism of 45–60% of all currently used drugs. In addition to drugs, CYP3A isozymes metabolise a variety of other compounds including steroid hormones, toxins and carcinogens. It is also well known that the hepatic expression and activity of CYP3A isozymes varies from individual to individual. The involvement of this variability in harmful interactions frequently encountered in development and application of drugs that are CYP3A substrates is well documented. It has also been postulated that variable CYP3A expression could affect an individuals predisposition to cancers caused by environmental carcinogens that are metabolised by CYP3A. The elucidation of factors controlling an individuals CYP3A activity could permit personalised dose adjustments in therapies with its substrates and may also possibly lead to the identification of sub-populations at increased risk for several common cancers. However, until recently, the development of markers predictive for the individual CYP3A expression has been slower than for other drug metabolising enzymes. Here we summarise the current status of our understanding of the genetics and regulation of the expression of CYP3A, including the recently described markers of the CYP3A5 and CYP3A7 polymorphisms. These latter markers are expected to speed up the development of activity probes for the individual CYP3A isozymes and to aid in our understanding of their individual functions.     

Spatial and seasonal variability of the mass concentration and chemical composition of PM2.5 in Poland

The seasonal changes in ambient mass concentrations and chemical composition of fine particulate matter (PM_2.5) were investigated in three locations in Poland. The analyses included PM_2.5-bound hazardous benzo(a)pyrene (BaP), As, Ni, Cd, and Pb. The samples of PM_2.5 were collected daily in Katowice (southern Poland, urban background site), Gdańsk, and Diabla Góra (northern Poland, urban and regional background sites, respectively) during 1-year-long campaign in 2010. Based on monthly ambient concentrations of PM_2.5-bound carbon (organic and elemental), water-soluble ions (Na⁺, NH₄ ⁺, K⁺, Mg²⁺, Ca²⁺, Cl^?, NO₃ ^?, SO₄ ^2?), and elements As, Ni, Cd, Pb, Ti, Al, Fe, the chemical mass closure of PM_2.5 was checked for each of the four seasons of the year and for the heating and non-heating periods at each site. Also, the annual concentrations of PM_2.5 were determined and the annual PM_2.5 mass closure checked. At each measuring point, the PM_2.5 concentrations were high compared to its Polish yearly permissible value, 25 μg/m³, and its concentrations elsewhere in Europe. The highest annual PM_2.5 concentration, 43 μg/m³, occurred in Katowice; it was twice the annual PM_2.5 concentration in Gdańsk, and thrice the one in Diabla Góra. The high annual averages were due to very high monthly concentrations in the heating period, which were highest in the winter. PM_2.5 consisted mainly of carbonaceous matter (elemental carbon (EC) + organic matter (OM), the sum of elemental carbon, EC, and organic matter, OM; its annual mass contributions to PM_2.5 were 43, 31, and 33 % in Katowice, Gdansk, and Diabla Góra, respectively), secondary inorganic aerosol (SIA), the Na_Cl group, and crustal matter (CM)—in the decreasing order of their yearly mass contributions to PM_2.5. OM, EC, SIA, Na_Cl, and CM accounted for almost 81 % of the PM_2.5 mass in Katowice, 74 % in Gdańsk, and 90 % in Diabla Góra. The annual average toxic metal contribution to the PM_2.5 mass was not greater than 0.2 % at each site. In Katowice and Gdańsk, the yearly ambient BaP concentrations were high (15.4 and 3.2 ng/m³, respectively); in rural Diabla Góra, the concentrations of BaP were almost equal to 1 ng/m³, the Polish BaP annual limit. The great seasonal fluctuations of the shares of the component groups in PM_2.5 and of the concentrations of PM_2.5 and its components are due to the seasonal fluctuations of the emissions of PM and its precursors from hard and brown coal combustion for energy production, growing in a heating season, reaching maximum in winter, and decreasing in a non-heating period. In Gdańsk, northern Poland, especially in the spring and autumn, sea spray might have affected the chemical composition of PM_2.5. The greatest hazard from PM_2.5 occurs in Katowice, southern Poland, in winter, when very high concentrations of PM_2.5 and PM_2.5-related carbonaceous matter, including BaP, are maintained by poor natural ventilation in cities, weather conditions, and the highest level of industrialization in Poland. In less industrialized northern Poland, where the aeration in cities is better and rather gaseous than solid fuels are used, the health hazard from ambient PM_2.5 is much lower.     

Diplopia in Green Tobacco Sickness

ABSTRACT

This paper examines the first reported case of Green Tobacco Sickness (GTS) in Poland. A 25-year-old man who worked in a tobacco field for 14 hours with no protective measures experienced symptoms of GTS, and additionally, diplopia, after leaving the field. Upon hospital admission, diplopia was no longer observed. Diplopia was most probably caused by disturbances to the cholinergic neuromuscular transmission, secondary to nicotine. These neurological disturbances, the first of their kind observed in the course of GTS, deserve special attention. The case shows a potential adverse health effect related to tobacco harvest, as most Polish tobacco plantations are not mechanized. Polish farmers should be obligated to protect their workers with protective clothing, shoes, gloves and masks. Recommendations for tobacco harvester health are put forth in the paper.     

Fly agaric (Amanita muscaria) poisoning, case report and review.

Gathering and eating mushrooms and other plants containing psychoactive substances has become increasingly popular among young people experimenting with drugs. Dried fly agaric Amanita muscaria fruiting bodies were eaten by five young persons (18-21 years of age) at a party in order to evoke hallucinations. Visual and auditory hallucinations occurred in four of them, whereas a 18-year-old girl lost consciousness. The following morning, she went to the Clinic of Toxicology. Due to the fact that not all the active substances present in the fly agaric have been identified, and some of them have an effect after a period of latency, the patient was admitted for several days of observation during which check-up examinations were performed. After four days without any problems, she was discharged. The poisoning regressed with no organ complications. The remaining persons who had eaten the fly agaric were free from any complaints.     

Kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions

The kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions at 313, 323, 333 and 353 K over the pH-range 0.4-9.7 has been investigated. The decomposition was followed by the HPLC method. The pH-rate profile was accounted for by the specific acid- and base-catalysed reactions and also by assuming spontaneous or water-catalysed decomposition of both dissociated and undissociated molecules of diltiazem. Various buffer substances were found to exhibit general acid and base catalysis of the degradation. Thermodynamic parameters of the reaction: energy and enthalpy of activation and the frequency factor for the specific rate constants were determined.     

Short-term effects of angiotensin II receptor blockade in patients with primary glomerulonephritis: pilot study.

OBJECTIVE: There is evidence that angiotensin II, the main effector of renin-angiotensin system, plays a crucial role in the pathogenesis of chronic renal injury. Angiotensin II type 1 (AT-1) receptor blockers reduce renin-angiotensin system activity by blocking the receptor, the activation of which is responsible for the majority of deleterious angiotensin II effects. The aim of the present study was to investigate renal and metabolic effects of specific AT-1 receptor blocker-losartan in patients with primary glomerulonephritis. DESIGN: Pilot clinical study. SETTING: Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland. PARTICIPANTS: Fifteen patients aged 43.3 +/- 11.3 years with primary glomerulonephritis confirmed by renal biopsy were studied. INTERVENTION: Creatinine clearance, urinary excretion of protein and uric acid, urinary activity of N-acetyl-beta-D-glucosaminidase, and serum concentrations of lipids, protein, and uric acid were evaluated before and after 3 months of losartan (Cozaar; Merck Sharp & Dohme, Harlow, Essex, United Kingdom) treatment at a dose of 25 mg daily. RESULTS: We found a significant reduction of urinary excretion of protein (P <.008; average, 32%). Results also revealed a decrease of serum uric acid level (P <.01), probably as a consequence of elevated uric acid urinary excretion (P <.09). No significant changes in creatinine clearance, N-acetyl-beta-D-glucosaminidase activity, protein, or lipid levels were observed. CONCLUSION: We concluded that losartan treatment at a small dose of 25 mg daily produces antiproteinuric effect without adverse effects, notably with no decrease of glomerular filtration, and simultaneously induces beneficial changes in purine metabolism.