In vitro algaecide effect of sodium hypochlorite and iodine based antiseptics on Prototheca zopfii strains isolated from bovine milk

Prototheca zopfii has been considered one of the most important causes of environmental mastitis in Brazil. These algae are refractory to conventional therapy and cause great damage to the mammary gland. The present study evaluated the in vitro algaecide effect of sodium hypochlorite and iodine based antiseptics on 27 P. zopfii strains isolated from the milk of cattle. Low concentrations of sodium hypochlorite (0.0390625-0.15625%) and iodine (0.15625-0.625%) were effective against the isolates. These antiseptics may be recommended for hygiene routines, pre and postdipping and cauterization of bovine mammary glands infected by P. zopfii. (C) 2009 Elsevier Ltd. All rights reserved.

Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease

Background Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD). Objective The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD. Methods Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD. Results UAC in dogs with CKD (range, 0.002-7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005-0.01; median, 0.002). Microalbuminuria (UAC 0.03-0.3) and macroalbuminuria (UAC > 0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure >= 180 mmHg; in these dogs, UAC ratio (range, 0.006-7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure < 180 mmHg (range, 0.002-4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC > 1.0 usually had macroalbuminuria, those with UPC 0.5-1.0 usually had microalbuminuria, and those with UPC < 0.5 usually lacked albuminuria. Conclusions UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC < 1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

Periodontal attachment loss in an untreated isolated population of Brazil

Background: The aim of this study was to assess the prevalence, extent, and severity of clinical attachment loss (CAL) and to investigate the association of demographic, socioeconomic, and behavioral risk indicators with CAL in an untreated isolated population in Brazil. Methods: All subjects aged >= 12 years were identified by a census. Participants were submitted to a full-mouth clinical examination of six sites per tooth and were interviewed using a structured, written questionnaire. Results: Among the 214 subjects who were interviewed and examined clinically, CAL >= 5 mm in at least one site was observed in 8% of the 12- to 19-year-olds and in all dentate subjects >= 50 years of age; the age-dependent prevalence of CAL >= 7 mm in at least one site ranged from 5% among 12- to 19-year-olds to 83% among subjects >= 50 years old. Multivariate analysis identified plaque (odds ratio [OR] = 2.8), supragingival calculus (OR = 2.9 to 10.6), age >= 30 years (OR = 11.4), and smoking (OR = 2.4) as risk indicators for CAL >= 5 mm and smoking (OR = 8.2) as a risk indicator for CAL >= 7 mm. Conclusions: CAL is highly prevalent in this isolated population. The high occurrence of CAL in young age groups and the confirmation of traditional risk indicators for CAL in this study suggest that other factors, such as host susceptibility, may be needed to explain the high levels of CAL found. Age and behavioral factors were risk indicators associated significantly with the CAL found in this population and may be useful indicators of high-risk subjects for periodontal diseases.

Tooth loss prevalence and risk indicators in an isolated population of Brazil

Objective. The aim of this study was to assess the prevalence, extent, and risk indicators of tooth loss in an isolated population of Brazil. Material and methods. Two-hundred-and-forty-two subjects, ranging in age from 14 to 82 years (mean 36.2 years), were identified by census in an isolated population of Brazil. All consenting subjects received a full-mouth clinical (DFT index and information about missing teeth) and periodontal examination of 6 sites per tooth. Furthermore, they were interviewed using a structured written questionnaire in order to gather information about demographic, environmental, and biological variables. Results. Of the 200 subjects (80% response rate), 19 (9.5%) were edentulous, 90% had lost at least one tooth, and 39% had lost more than 8 teeth. The mean number of teeth lost was 9.5 (95% CI = 8.2-10.8). First mandibular molars were the most commonly missing teeth. In a multiple logistic regression analysis based on a theoretical hierarchical model of tooth loss, having more than 8 teeth lost was strongly associated with adult age (OR = 18.3-17.3, 95% CIs = 4.8-69.7 and 4.0-75.1) and female gender (OR = 5.9, 95% CI = 1.9-18.2) in the final model. Conclusions. Tooth loss was highly prevalent and extensive in this isolated population. Demographic and behavioral factors played an important role in tooth loss prevalence in this population.

Risk indicators for increased probing depth in an isolated population in Brazil

Background: The aim of this study was to assess the prevalence, extent, and severity of probing depth (PD) and to investigate the associations between demographic, socioeconomic, and behavioral risk indicators and PD in a periodontally untreated and isolated population in Brazil. Methods: The target population consisted of all individuals aged >= 12 years as identified by a census. Consenting participants were submitted to a full-mouth clinical examination of six sites per tooth and were interviewed using a structured written questionnaire. Results: Among the 214 subjects who were interviewed and clinically examined, PD >= 4 mm was observed in 54% to 83% of the subjects, depending on age, whereas the age-dependent prevalence of PD :6 mm ranged from 5% among 12- to 19-year-olds to 50% among 40- to 49-year-olds, decreasing to 40% among subjects >= 50 years of age. Multivariate analyses identified supragingival calculus (odds ratio [OR] = 5.4 to 10.3; 95% confidence intervals [CIs]: 2.5 to 11.6 and 4.0 to 26.2 for 20% to 50% and > 50% of the sites, respectively) as a risk indicator for PD A mm, whereas age :40 years (OR = 9.0; 95% CI: 1.7 to 48.5), being a moderate/heavy smoker (OR = 3.7; 95% CI: 1.4 to 10. 1), and having supragingival calculus in 20% to 50% of sites (OR = 6.8; 95% CI: 1.4 to 32.4) or in >50% of sites (OR = 15.3; 95% CI: 3.2 to 73.6) were risk indicators for PD >= 6 mm. Having undergone urgency dental treatment was a protective factor for PD A and >= 6 mm (OR = 0.4; 95% CI: 0.2 to 0.8). Conclusions: Increased PD is highly prevalent in this isolated population. Behavioral factors played a significant role as risk indicators for increased PD in this isolated population.

Bite force, electromyography, and mandible mobility during the 6-month period after surgical treatment for isolated fractures of the zygomatico-orbital complex

Objective. The aim of this study was to identify the behavior of masticatory muscles after fractures of the zygomatico-orbital complex (ZOC) and subsequent surgical treatment, by using analyses of bite force, electromyography (EMG), and mandible mobility during a 6-month period after surgery. Study design. Five patients with fractured ZOCs treated surgically by using an intraoral approach and fixation exclusively in the region of the zygomaticomaxillary buttress were evaluated. The control group included 12 other patients. During postoperative follow-up, bite force, mandible mobility, and EMG analysis of the masticatory muscles were evaluated. Results. There was an increase in bite force with time, but a decline in EMG activity during the same period. In the mandible mobility analysis, only maximum mouth-opening values increased significantly after the surgical treatment. Conclusions. The masticatory musculature, according to bite force and EMG, returned to its normal condition by the second month after surgery, and maximum mouth opening was observed after the first month. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111:e1-e7)

Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling

Structural vascular changes in two-kidney, one-clip (2K-1C) hypertension may result from increased matrix metalloproteinase (MMP)-2 activity. MMP-2 activation is regulated by other MMPs, including transmembrane-MMPs, and by tissue inhibitors of MMPs (TIMPs). We have investigated the localization of MMP-2, -9, -14, and TIMPs 1-4 in hypertensive aortas and measured their levels by zymography/Western blotting and immunohistochemistry. Gelatinolytic activity was assayed in tissues by in situ zymography. Sham-operated and 2K-1C hypertensive rats were treated with doxycycline (or vehicle) for 8 weeks, and the systolic blood pressure was monitored weekly. Doxycycline attenuated 2K-1C hypertension (165 +/- 11.7 mmHg versus 213 +/- 7.9 mm Hg in hypertensive controls, P<0.01), and completely prevented increase in the thicknesses of the media and the intima in 2K-1C animals (P<0.01). Increased amounts of MMP-2, -9, and -14 were found in hypertensive aortas, as well as enhanced gelatinolytic activity. A gradient in the localization of MMP-2, -9, and -14 was found, with increased amounts detected in the intima, at sites with higher gelatinolytic activity. Doxycycline attenuated hypertension induced increases in all the 3 investigated MMPs in both the media and the intima (all P<0.05). but it did not change the amounts of TIMPs 1-4 (P>0.05). Therefore, an imbalance between increased amounts of MMPs at the tissue level without a corresponding increase in the quantities of TIMPs, particularly in the intima and inner media layers, appears to account for the increased proteolytic activity found in 2K-1C hypertension-induced maladaptive vascular remodeling. (C) 2009 Elsevier B.V. All rights reserved.

Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension

Pulmonary vascular remodeling is an important pathological feature of pulmonary hypertension, leading to increased pulmonary vascular resistance and reduced compliance. It involves thickening of all three layers of the blood vessel wall (due to hypertrophy and/or hyperplasia of the predominant cell type within each layer), as well as extracellular matrix deposition. Neomuscularisation of non-muscular arteries and formation of plexiform and neointimal lesions also occur. Stimuli responsible for remodeling involve transmural pressure, stretch, shear stress, hypoxia, various mediators [angiotensin II, endothelin (ET)-1, 5-hydroxytryptamine, growth factors, and inflammatory cytokines], increased serine elastase activity, and tenascin-C. In addition, there are reductions in the endothelium-derived antimitogenic substances, nitric oxide, and prostacyclin. Intracellular signalling mechanisms involved in pulmonary vascular remodeling include elevations in intracellular Ca2+ and activation of the phosphatidylinositol pathway, protein kinase C, and mitogen-activated protein kinase. In animal models of pulmonary hypertension, various drugs have been shown to attenuate pulmonary vascular remodeling. These include angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, ET receptor antagonists, ET-converting enzyme inhibitors, nitric oxide, phosphodiesterase 5 inhibitors, prostacyclin, Ca2+-channel antagonists, heparin, and serine elastase inhibitors. Inhibition of remodeling is generally accompanied by reductions in pulmonary artery pressure. The efficacy of some of the drugs varies, depending on the animal model of the disease. In view of the complexity of the remodeling process and the diverse aetiology of pulmonary hypertension in humans, it is to be anticipated that successful anti-remodeling therapy in the clinic will require a range of different drug options. (C) 2001 Elsevier Science Inc. All rights reserved.

Pulmonary Vascular remodelling in hypoxic rats: effects of amlodipine, alone and with perindopril

This study investigated whether pulmonary Vascular remodelling in hypoxic pulmonary hypertensive rats (10% oxygen; 4 weeks) could be prevented by treatment, during hypoxia, with amlodipine (IO mg/kg/day, p.o.), either alone or in combination with the angiotensin converting enzyme inhibitor, perindopril (30 mg/kg/day, p.o.). Medial thickening of pulmonary arteries (30-500 mum o.d.) was attenuated by amlodipine whereas it was totally prevented by the combination treatment (amlodipine plus perindopril); neomuscularisation of small alveolar arteries (assessed from critical closing pressure in isolated perfused lungs) was not affected. Pulmonary vascular resistance (isolated perfused lungs) was reduced by both treatment regimes but only combination treatment reduced right ventricular hypertrophy. Taus, amlodipine has anti-remodelling properties in pulmonary hypertensive rats. The finding that combining amlodipine with another anti-remodelling drug produced effects on vascular structure that were additive raises the question of whether combination therapy with two different anti-remodelling drugs may be of value in the treatment of patients with hypoxic (and possibly other forms of) pulmonary hypertension. (C) 2001 Elsevier Science B.V. All rights reserved.

Properties and function of KCNQ1 K+ channels isolated from the rectal gland of Squalus acanthias

KCNQ1 (K(V)LQT1) K+ channels play an important role during electrolyte secretion in airways and colon. KCNQ1 was cloned recently from NaCl-secreting shark rectal glands. Here we study. the properties and regulation of the cloned sK(V)LQT1 expressed in Xenopus oocytes and Chinese hamster ovary (CHO) cells and compare the results with those obtained from in vitro perfused rectal gland tubules (RGT). The expression of sKCNQ1 induced voltage-dependent, delayed activated K+ currents, which were augmented by an increase in intracellular cAMP and Ca2+. The chromanol derivatives 293B and 526B potently inhibited sKCNQ1 expressed in oocytes and CHO cells, but had little effect on RGT electrolyte transport. Short-circuit currents in RGT were activated by alkalinization and were decreased by acidification. In CHO cells an alkaline pH activated and an acidic pH inhibited 293B-sensitive KCNQ1 currents. Noise analysis of the cell-attached basolateral membrane of RGT indicated the presence of low-conductance (

Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: Transmembrane exchange and cytoplasmic binding process

This work studied the structure-hepatic disposition relationships for cationic drugs of varying lipophilicity using a single-pass, in situ rat liver preparation. The lipophilicity among the cationic drugs studied in this work is in the following order: diltiazem. propranolol. labetalol. prazosin. antipyrine. atenolol. Parameters characterizing the hepatic distribution and elimination kinetics of the drugs were estimated using the multiple indicator dilution method. The kinetic model used to describe drug transport (the two-phase stochastic model) integrated cytoplasmic binding kinetics and belongs to the class of barrier-limited and space-distributed liver models. Hepatic extraction ratio (E) (0.30-0.92) increased with lipophilicity. The intracellular binding rate constant (k(on)) and the equilibrium amount ratios characterizing the slowly and rapidly equilibrating binding sites (K-S and K-R) increase with the lipophilicity of drug (k(on) : 0.05-0.35 s(-1); K-S : 0.61-16.67; K-R : 0.36-0.95), whereas the intracellular unbinding rate constant (k(off)) decreases with the lipophilicity of drug (0.081-0.021 s(-1)). The partition ratio of influx (k(in)) and efflux rate constant (k(out)), k(in)/k(out), increases with increasing pK(a) value of the drug [from 1.72 for antipyrine (pK(a) = 1.45) to 9.76 for propranolol (pK(a) = 9.45)], the differences in k(in/kout) for the different drugs mainly arising from ion trapping in the mitochondria and lysosomes. The value of intrinsic elimination clearance (CLint), permeation clearance (CLpT), and permeability-surface area product (PS) all increase with the lipophilicity of drug [CLint (ml . min(-1) . g(-1) of liver): 10.08-67.41; CLpT (ml . min(-1) . g(-1) of liver): 10.80-5.35; PS (ml . min(-1) . g(-1) of liver): 14.59-90.54]. It is concluded that cationic drug kinetics in the liver can be modeled using models that integrate the presence of cytoplasmic binding, a hepatocyte barrier, and a vascular transit density function.

Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat

Nude rats bearing melanomas on their hindlimbs were treated by isolated limb infusion (ILI) with increasing doses (7.5-400 mug/ml) of melphalan. The response of tumours to treatment at the end of the observation period was graded, according to diameter, as complete response (CR), partial response (PR), no change (NC) or progressive disease (PD). No linear relationship between the dose of melphalan and the tumour response was observed. All doses above a threshold of 15 mug/ml achieved a PR or CR. The achievement of CR was not related to increased dose. Two major implications arise from this work. Firstly, the typically two-to three-fold increase in cytotoxic drug concentration given in high dose chemotherapy compared with standard drug concentration may not be sufficient to produce the expected increase in tumour response and possibly survival, and the controversial results of high dose chemotherapy in different studies may thus be explained. Secondly, since an increase in melphalan dose above a certain threshold does not greatly increase tumour response, the use of combination therapies would seem to be more likely to be effective than increased chemotherapeutic drug doses in achieving better tumour responses.

Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy

Isolated limb infusion (ILI) is an attractive, less complex alternative to Isolated limb perfusion (ILP). It has a lower morbidity in treating localized recurrences and in transit metastases of the limb for tumours such as melanoma, Merkel cell tumour and Kaposi's sarcoma, allowing administration of high concentrations of cytotoxic agent to the affected limb under hypoxic conditions. Melphalan is the preferred cytotoxic agent for the treatment of melanoma by ILP or ILI. We report pharmacokinetic data from 12 patients treated by ILI for tumours of the limb in Brisbane. The kinetics of drug distribution in the limb was calculated using a two-compartment vascular model, where both tissue and infusate act as well-stirred compartments. Analysis of melphalan concentrations in the perfusate during ILI showed good agreement between the values measured and the concentrations predicted by the model. Recirculation and wash-out flow rates, tissue concentrations and the permeability surface area product (PS) were calculated. Correlations between the PS value and the drug concentrations In the perfusate and tissue were supported by the results. These data contribute to a better understanding of the distribution of melphalan during ILI in the limb, and offer the opportunity to optimize the drug regimen for patients undergoing ILI. (C) 2001 Lippincott Williams & Wilkins.