Ketoprofen-loaded rose hip oil nanocapsules attenuate chronic inflammatory response in a pre-clinical trial in mice.

This study aimed to develop nanocapsules containing ketoprofen using rose hip oil (Keto-NC) as oil core, and to evaluate their anti-inflammatory activity in acute and chronic ear edema models in mice. Physicochemical characterization, drug release, photostability and cytotoxicity assays were performed for the developed Keto-NC formulations and compared to ketoprofen-loaded nanocapsules using medium chain triglycerides as oil core (Keto-MCT-NC). Anti-inflammatory activity of orally delivered KP (Ketoprofen-free; 10 mg.kg-1) or Keto-NC (2.5; 5; 10 mg.kg-1) was assessed in mouse acute and chronic ear edema induced by croton oil (CO). Edema histological characteristics were determined by H&E stain, and redox parameters were analyzed in blood plasma and erythrocytes. Keto-MCT-NC and Keto-NC did not exhibit differences regarding physicochemical parameters, including size diameters, polydispersity index, pH, Ketoprofen content, and encapsulation efficiency. However, Keto-NC, which contains rose hip oil as lipid core, decreased drug photodegradation under UVC radiation when compared to Keto-MCT-NC. KP or Keto-NC were not cytotoxic to keratinocyte cultures and produced equal edema inhibition in the acute protocol. Conversely, in the chronic protocol, Keto-NC was more effective in reducing edema (~60-70% on 7-9th days of treatment) when compared to KP (~40% on 8-9th days of treatment). This result was confirmed by histological analysis, which indicated reduction of edema and inflammatory infiltrate. A sub-therapeutic dose of Keto-NC (5 mg.kg-1) significantly reduced edema when compared to control. Finally, KP and Keto-NC exhibited similar effects on redox parameters, suggesting that the advantages associated with Ketoprofen nanoencapsulation did not involve oxidative stress pathways. The results showed that Keto-NC was more efficient than KP in reducing chronic inflammation. These data may be important for the development of strategies aiming treatment of chronic inflammatory diseases with fewer adverse effects.

Physical properties of films based on pectin and babassu coconut mesocarp.

The objective of this research was to study the physical properties, water sorption, thermal and structure of films made from citrus pectin (CP), babassu coconut mesocarp (BCM) and glycerol (G). Seventeen formulations were prepared according to a central compound rotational design combining different proportions of the materials and evaluating the films produced according to their moisture contents, solubility, thicknesses and water vapor permeability. The results showed a direct relationship between the composition of the film and each physical property, providing films with unique mechanical characteristics and barrier properties. In the second phase, the films were reformulated, maintaining the proportions of CP and BCM constant and altering the G content. The results showed films with permeable structures, thus favoring the use of high drying temperatures (up to 70 °C) for the confection of films, without altering their physical and structural properties.

Antimicrobial alumina nanobiostructures of disulfide- and triazole-linked peptides: Synthesis, characterization, membrane interactions and biological activity.

Due to the its physical-chemical properties, alumina nanoparticles have potential applications in several areas, such as nanobiomaterials for medicinal or orthodontic implants, although the introduction of these devices poses a serious risk of microbial infection. One convenient strategy to circumvent this problem is to associate the nanomaterials to antimicrobial peptides with broad-spectrum of activities. In this study we present two novel synthesis approaches to obtain fibrous type alumina nanoparticles covalently bound to antimicrobial peptides. In the first strategy, thiol functionalized alumina nanoparticles were linked via disulfide bond formation to a cysteine residue of an analog of the peptide BP100 containing a four amino acid spacer (Cys-Ala-Ala-Ala). In the second strategy, alumina nanoparticles were functionalized with azide groups and then bound to alkyne-decorated analogs of the peptides BP100 and DD K through a triazole linkage obtained via a copper(I)-catalyzed cycloaddition reaction. The complete physical-chemical characterization of the intermediates and final materials is presented along with in vitro biological assays and membrane interaction studies, which confirmed the activity of the obtained nanobiostructures against both bacteria and fungi. To our knowledge, this is the first report of aluminum nanoparticles covalently bound to triazole-peptides and to a disulfide bound antimicrobial peptide with high potential for biotechnological applications.

Nanobiostructure of fibrous-like alumina functionalized with an analog of the BP100 peptide: Synthesis, characterization and biological applications.

The functionalization of alumina nanoparticles of specific morphology with antimicrobial peptides (AMP) can be a promising strategy for modeling medical devices and packaging materials for cosmetics, medicines or food, since the contamination by pathogens could be reduced. In this paper, we show the synthesis of a fibrous-like alumina nanobiostructure, as well as its functionalization with the peptide EAAA-BP100, an analog of the antimicrobial peptide BP100. The antibacterial activity of the obtained material against some bacterial strains is also investigated. The covalent binding of the peptide to the nanoparticles was promoted by a reaction between the carboxyl group of the glutamate side chain (E1) of the peptide and the amino groups of the alumina nanoparticles, previously modified by reaction with 3-aminopropyltrietoxysilane (APTES). The functionalized nanoparticles were characterized by zeta potential measurements, Fourier transform infrared spectroscopy, and other physicochemical techniques. Although the obtained alumina nanobiostructure shows a relatively low degree of substitution with EAAA-BP100, antibacterial activities against Escherichia coli and Salmonella typhimurium strains are appreciably higher than the activities of the free peptide. The obtained results can affect the design of new hybrid nanobiomaterials based on nanoparticles functionalized with AMP.

Acute hemodynamic and electrocardiographic responses to a session of inspiratory muscle training in cardiopulmonary rehabilitation.

BACKGROUND: Inspiratory muscle training (IMT) has been shown to generate significant benefits in different clinical conditions; however, there is scarce information regarding acute clinical and hemodynamic effects. AIM: The aim of this study was to evaluate clinical, hemodynamic and electrocardiographic responses during a single short IMT session in patients enrolled in cardiopulmonary rehabilitation program (CRP). DESIGN: Cross-sectional study. SETTING: Patients referred and regularly attending a non-hospital based medically-supervised exercise program. POPULATION: One hundred and sixty patients patients who regularly performed inspiratory muscle training METHODS: A convenience sample of 21 elderly patients (16 men; 60-87 years of age) had an ECG continuously recorded and heart rate (HR) and blood pressure (BP) measured before, during and one-minute after a single IMT session - two sets of 15 cycles with one-minute interval. RESULTS: Comparing values obtained before, during second set and one-minute after IMT, no differences were found to HR (bpm) - 68±2 vs. 70±2 vs. 66±3 (P=0.05) and in systolic and diastolic BP (mm Hg) values, respectively, - 105±3 vs. 111±4 vs. 108±3 (P=0.06) and - 68±2 vs. 72±3 vs. 68±2 (P=0.14); (before, during second set and one-minute after TMI). During IMT, seven (33%) of patients presented minor cardiac arrhythmias, most of them isolated premature ventricular contractions. Additionally, no abnormal signs or symptoms were found. CONCLUSION: Apart of minor and clinically irrelevant ECG abnormalities seen in 1/3 of the patients, a short IMT session did not induce significant hemodynamic responses or relevant clinical abnormalities. Based on these results, for elderly patients involved in CPR, IMT seems to be clinically safe and continuous ECG monitoring did not seem to add significant or relevant information. CLINICAL REHABILITATION IMPACT: For elderly patients participating in CPR, short IMT sessions do not induce major hemodynamic responses and seem to be clinically safe. This is potentially useful information if IMT is to be prescribed in home-based programs.

The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth.

OBJECTIVE: The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. STUDY DESIGN: In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. RESULT: Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (ß=0.165; 95% confidence interval (CI): 0.031-0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (ß=0.021; 95% CI: 0.002-0.041; P=0.034) and percentage of fat mass (ß=0.636; 95% CI: 0.125-1.147; P=0.016) in female offspring were found. CONCLUSION: Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.

Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania amazonensis.

Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania which affects 12 million people worldwide. The discovery of drugs for the treatment of leishmaniasis is a pressing concern in global health programs. The aim of this study aim was to evaluate the leishmanicidal effect of piperine and its derivatives/analogues on Leishmania amazonensis. Our results showed that piperine and phenylamide are active against promastigotes and amastigotes in infected macrophages. Both drugs induced mitochondrial swelling, loose kinetoplast DNA, and led to loss of mitochondrial membrane potential. The promastigote cell cycle was also affected with an increase in the G1 phase cells and a decrease in the S-phase cells, respectively, after piperine and phenylamide treatment. Lipid analysis of promastigotes showed that piperine reduced triglyceride, diacylglycerol, and monoacylglycerol contents, whereas phenylamide only reduced diacylglycerol levels. Both drugs were deemed non toxic to macrophages at 50 µM as assessed by XTT (sodium 2,3,-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium inner salt), Trypan blue exclusion, and phagocytosis assays, whereas low toxicity was noted at concentrations higher than 150 µM. None of the drugs induced nitric oxide (NO) production. By contrast, piperine reduced NO production in activated macrophages. The isobologram analysis showed that piperine and phenylamide acted synergistically on the parasites suggesting that they affect different target mechanisms. These results indicate that piperine and its phenylamide analogue are candidates for development of drugs for cutaneous leishmaniasis treatment.

Early high calcium and phosphorus intake by parenteral nutrition prevents short-term bone strength decline in preterm infants.

BACKGROUND AND AIM: Very premature newborns have an increased risk of low bone mass and metabolic bone disease. Most longitudinal studies report a significant decline in bone strength in the first weeks after birth. The aim of the study was to evaluate whether higher early calcium (Ca) and phosphorus (P) intake delivered by parenteral nutrition (PN) can prevent bone strength decline in preterm infants, within the first weeks after birth. PATIENTS AND METHODS: This was a randomized controlled trial of consecutively admitted neonates born with ≤ 33 weeks of gestational age, assigned to receive either Ca 45 mg · kg⁻¹ · day⁻¹ (low dose [LD]) or Ca 75 mg · kg⁻¹ · day⁻¹ (high dose [HD]) by PN. P was added to the PN solutions at a fixed Ca:P ratio (mg) of 1.7:1. Bone strength was assessed by the speed of sound (SOS) using the quantitative ultrasound method. Measurements were performed weekly from birth until discharge. Low bone strength (SOS < 10th centile of reference values) was the main outcome. RESULTS: Eighty-six infants were enrolled, 40 assigned to LD group and 46 to HD group. Mean (standard error) gestational age was 29.6 weeks (2.1) and birth weight was 1262 g (0.356). In the HD group, the SOS values never fell below those recorded at birth and, up to the sixth week of life, low bone strength was significantly less frequent as compared with that in the LD group, in spite of progressive reduction in parenteral mineral intake and/or establishment of full enteral feeding. CONCLUSIONS: Early assigned parenteral intake of Ca 75 mg · kg⁻¹ · day⁻¹ and P 44 mg · kg⁻¹ · day⁻¹ significantly contributed to preventing short-term bone strength decline in preterm infants.

Croton sonderianus essential oil samples distinctly affect rat airway smooth muscle.

Plants of the genus Croton have been used extensively in the northeast of Brazil for treating various clinical conditions. Previous studies have demonstrated that the essential oil of some specimens of Croton sp. have a relaxing effect on tracheal smooth muscle. Our study aimed to characterize the effects of Croton sonderianus essential oil samples, collected at 1:00 pm (EO-13) and 9:00 pm (EO-21), on rat tracheal smooth muscle. The two samples were submitted to gas chromatography (GC) and mass spectrometry (MS) analysis to identify their components. Rat tracheal smooth muscle strips were used to assess the biological activity. The major constituents of EO-21 were: spathulenol (18.32%), beta-caryophyllene (14.58%) and caryophyllene oxide (8.54%) and the major constituents of EO-13 were bicyclogermacrene (16.29%), beta-phellandrene (15.42%) and beta-caryophyllene (13.82%). These samples showed an antispasmodic effect on tracheal smooth muscle strips pre-contracted with high K+ concentration (80 mM) or with acetylcholine. EO-21 increased baseline tonus while EO-13 provoked a decrease. These results demonstrated that EO-13 and EO-21 have different chemical composition and showed myorelaxant activity. In conclusion, EO-13 and EO-21 may have potential therapeutic use in the treatment of bronchospasm.

Transcutaneous electrical nerve stimulation at both high and low frequencies activates ventrolateral periaqueductal grey to decrease mechanical hyperalgesia in arthritic rats.

Transcutaneous electric nerve stimulation (TENS) is widely used for the treatment of pain. TENS produces an opioid-mediated antinociception that utilizes the rostroventromedial medulla (RVM). Similarly, antinociception evoked from the periaqueductal grey (PAG) is opioid-mediated and includes a relay in the RVM. Therefore, we investigated whether the ventrolateral or dorsolateral PAG mediates antinociception produced by TENS in rats. Paw and knee joint mechanical withdrawal thresholds were assessed before and after knee joint inflammation (3% kaolin/carrageenan), and after TENS stimulation (active or sham). Cobalt chloride (CoCl(2); 5 mM) or vehicle was microinjected into the ventrolateral periaqueductal grey (vlPAG) or dorsolateral periaqueductal grey (dlPAG) prior to treatment with TENS. Either high (100 Hz) or low (4 Hz) frequency TENS was then applied to the inflamed knee for 20 min. Active TENS significantly increased withdrawal thresholds of the paw and knee joint in the group microinjected with vehicle when compared to thresholds prior to TENS (P<0.001) or to sham TENS (P<0.001). The increases in withdrawal thresholds normally observed after TENS were prevented by microinjection of CoCl(2) into the vlPAG, but not the dlPAG prior to TENS and were significantly lower than controls treated with TENS (P<0.001). In a separate group of animals, microinjection of CoCl(2) into the vlPAG temporarily reversed the decreased mechanical withdrawal threshold suggesting a role for the vlPAG in the facilitation of joint pain. No significant difference was observed for dlPAG. We hypothesize that the effects of TENS are mediated through the vlPAG that sends projections through the RVM to the spinal cord to produce an opioid-mediated analgesia.

Osmolality of elemental and semi-elemental formulas supplemented with nonprotein energy supplements.

BACKGROUND: Elemental and semi-elemental formulas are used to feed infants with short bowel syndrome, who may not be able to tolerate feeds of more than 310 mOsm kg(-1). The present study aimed to measure the osmolality of elemental and semi-elemental formulas at different concentrations, with and without the addition of nonprotein energy supplements. METHODS: The osmolality of one elemental and three semi-elemental formulas was measured by the freezing point depression method at concentrations of 10, 12, 14 and 16 g per 100 mL, with and without 10% or 20% of additional calories, in the form of glucose polymers and medium chain triglycerides. Inter-analysis and intra-analysis coefficients of variation of the measurements were less than 3.9%. RESULTS: The mean osmolalities of formulas reconstituted up to 12 g per 100 mL did not exceed 305.3 mOsm kg(-1), even with added energy supplements. The mean osmolalities of formulas at 14 and 16 g per 100 mL, with or without added energy supplements varied between 205.8 and 421.6 mOsm kg(-1). CONCLUSIONS: A comprehensive list of elemental and semi-elemental formulas at different concentrations, enriched or not with calories, is made available. This will enable professionals to customize feeds with the optimum composition, without exceeding the osmolality suggested for infants with short bowel syndrome.

Unequivocal NMR assignments: O-methoxy-methyl esters derivatives of acid chromanones from Calophyllum brasiliense CAMB. (Guanandi).

The present work describes the fractionation of the crude hexane extract (EBHEX) from Calophyllum brasiliense (Clusiaceae) stem bark. Derivatization of DCM(2-9) fraction with diazomethane afforded the chromanones inophylloidic acid, isobrasiliensic acid, as well as, a mixture containing isobrasiliensic and brasiliensic acids, in the form of their more stable O-methoxy-methyl esters derivatives 1, 2, and 3, respectively. The isolation of 1 from C. brasiliense is described for the first time herein. The use of two-dimensional NMR methods ((1)H-COSY, HMQC, and HMBC) allowed the precise determination of (13)C and (1)H chemical shifts of compounds 1, 2, and 3.

Osmolality of preterm formulas supplemented with nonprotein energy supplements.

BACKGROUND: Addition of energy supplements to preterm formulas is an optional strategy to increase the energy intake in infants requiring fluid restriction, in conditions like bronchopulmonary dysplasia. This strategy may lead to an undesirable increase in osmolality of feeds, the maximum recommended safe limit being 400 mOsm/kg. The aim of the study was to measure the changes in osmolality of several commercialized preterm formulas after addition of glucose polymers and medium-chain triglycerides. METHODS: Osmolality was measured by the freezing point depression method. Six powdered formulas with concentrations of 14 g/100 ml and 16 g/100 ml, and five ready-to-feed liquid formulas were analyzed. All formulas, were supplemented with 10% (low supplementation) or 20% (high supplementation) of additional calories, respectively, in the form of glucose polymers and medium chain triglycerides, maintaining a 1:1 glucose:lipid calorie ratio. Inter-analysis and intra-analysis coefficients of variation of the measurements were always < 3.9%. RESULTS: The mean osmolality (mOsm/kg) of the non-supplemented formulas varied between 268.5 and 315.3 mOsm/kg, increasing by 3-5% in low supplemented formulas, and by 6-10% in high supplemented formulas. None of the formulas analyzed exceeded 352.8 mOsm/kg. CONCLUSION: The supplementation of preterm formulas with nonprotein energy supplements with up to 20% additional calories did not exceed the maximum recommended osmolality for neonatal feedings.

Excitatory amino acid receptors in the periaqueductal gray mediate the cardiovascular response evoked by activation of dorsomedial hypothalamic neurons.

Neurons in the region of dorsomedial hypothalamus are involved in the organization of the physiological responses to emotional stress. We have recently shown that the cardiovascular response evoked by activation of dorsomedial hypothalamus neurons is largely dependent on a synaptic relay with the lateral/dorsolateral periaqueductal gray region. In this study, we aimed to investigate whether excitatory amino acid receptors at the lateral/dorsolateral periaqueductal gray region are involved in mediating the response evoked by activation of dorsomedial hypothalamus neurons. In conscious rats, the cardiovascular effects produced by microinjection of GABA(A) receptor antagonist, bicuculline methiodide into the dorsomedial hypothalamus were evaluated before and after injection of different excitatory amino acid antagonists into lateral/dorsolateral periaqueductal gray region. Pretreatment of lateral/dorsolateral periaqueductal gray region with the non-selective ionotropic excitatory amino acid receptor antagonist kynurenic acid or with the N-methyl-D-aspartate receptor-selective antagonist, MK-801, largely reduced the tachycardic and pressor effects evoked by activation of dorsomedial hypothalamus neurons by bicuculline methiodide microinjection (heart rate 90 and 74%; blood pressure 81 and 84%, respectively). The non-N-methyl-D-aspartate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, did not alter the cardiovascular response evoked by dorsomedial hypothalamus activation. In an additional series of experiments, microinjection of the N-methyl-D-aspartate receptor agonist, N-methyl-D-aspartate, into the lateral/dorsolateral periaqueductal gray region, evoked an increase in heart rate and a pressor response that was accompanied by an increase in locomotor activity. These effects were not altered by pretreatment of lateral/dorsolateral periaqueductal gray region neurons with 6-cyano-7-nitroquinoxaline-2,3-dione but were completely abolished by MK-801. Altogether, these findings indicate that the cardiovascular response evoked by dorsomedial hypothalamus activation involves a synaptic relay at the lateral/dorsolateral periaqueductal gray region that is mediated at least in large part by excitatory amino acid receptors, possibly N-methyl-D-aspartate receptors.

In vitro evaluation of the antimicrobial activity of a castor oil-based irrigant.

The antimicrobial activity of irrigating solutions--Endoquil (castor oil detergent), 2% chlorhexidine gluconate solution, and 0.5% NaOCl solution-was evaluated against gram-positive cocci (Micrococcus luteus, Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Streptococcus mutans, and Streptococcus sobrinus), gram-negative rods (Escherichia coli and Pseudomonas aeruginosa), and the yeast Candida albicans. Activity was evaluated using the two-layer agar diffusion technique. The base layer was obtained by pouring 10.0 ml of Muller Hinton Medium or 10.0 ml of Brain Heart Infusion agar in a Petri dish. After solidification a 5.0 ml seed layer of Muller Hinton Medium or Brain Heart Infusion agar with inoculum (106/ml) was added. Absorbent paper disks (6.0 mm in diameter) immersed in the solutions were placed at equidistant points. Plates were maintained at room temperature for 2 h for prediffusion of the solutions and incubated at 37 degrees C for 24 h. The candle jar system was used for the Brain Heart Infusion agar plates. All tests were performed in duplicate. After incubation the medium was optimized with 0.05 g% triphenyltetrazolium chlorate gel and inhibition halos were measured. All bacterial strains were inhibited by 2.0% chlorhexidine gluconate. Endoquil was effective against gram-positive microorganisms, and 0.5% NaOCl was effective only against S. aureus.

HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats.

Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts of muscle contractions, it was suggested that, when this production exceeds the antioxidant capacity, the preexisting antioxidant pathways may be complemented by the synthesis of the defense mechanism represented by heat shock proteins (HSPs), stress proteins with the function of repair and maintaining protein folding. To test this hypothesis, we analyzed reactive carbonyl derivatives in plasma and the expression of HSP72 and activities of enzymes from the oxidative and antioxidant defense systems in the soleus muscle of sedentary rats and rats trained by two protocols: continuous and intermittent. We analyzed all three groups at rest and 2 h after acute exercise. After 8 wk of training, the animals from both groups clearly demonstrated higher resistance to exercise. Both trained groups showed significantly higher citrate synthase, catalase, and glutathione reductase activities than the control group (P < 0.01). After acute exercise, catalase and glutathione reductase activities significantly decreased (P < 0.01) and plasma reactive carbonyl derivatives significantly increased (P < 0.05) in the sedentary group, suggesting an oxidative-stress condition as responsible for exhaustion in this group. Finally, after acute exercise, the induction of HSP72 expression occurred only in the sedentary group, suggesting that HSP72 acts as a complementary protective mechanism in exercise-induced oxidative stress.

[Rice and bean diets increase hepatic and plasmatic activity of gammaglutamyltranspeptidase in young rats]. / Dietas à base de arroz e feijão aumentam a atividade plasmática e hepática da gama-glutamiltranspeptidadase em ratos jovens.

The effect of feeding rice and bean diets in both hepatic and plasmatic activity of gamma-glutamyltranspeptidase-(GGT-EC 2.3.2.2) activity was evaluated in growing-rats (Experiment A) and mature rats (Experiment B). During 28 days, the animals were fed with isocaloric-diets composed by tree levels of rice, bean or rice-and-bean protein. Similarly with the aproteic group, a significant increase on both the hepatic and plasmatic GGT activity were showed with the lowest levels of protein, when compared with 25% casein control group. This rise was more effective in growing-rats fed on legume-based diets (as bean or rice-and-bean diets), making evident a differential effect of age and an exacerbated effect of the protein restriction with the lowest sulfur amino acids disposal. These alterations suggest a metabolic adaptation of GGT to both the inadequate protein and sulfur-amino acid levels, thus supporting the hypothesis that the Glutathione levels may be reduced by these legume-based diets.

Trihexyphenidyl and isoprinosine in the treatment of subacute sclerosing panencephalitis.

Six cases of subacute sclerosing panencephalitis (1 stage I, 3 stage II, 2 stage III) were diagnosed at our institution in the last 10 years. Five patients were treated with isoprinosine and the antiepileptic drug valproic acid. Three patients presented with myoclonic seizures refractory to valproic acid and the usual antiepileptic therapy. They received trihexyphenidyl with good results. We suggest the use of trihexyphenidyl in combination with isoprinosine in patients with subacute sclerosing panencephalitis with myoclonic seizures refractory to valproic acid.

Histopathological observations of periapical repair in teeth with radiolucent areas submitted to two different methods of root canal treatment.

Dogs' teeth with induced chronic periapical periodontitis were treated endodontically by two different methods, and the results were compared. A total of 40 root canals from the upper and lower premolars of two dogs were prepared chemomechanically. In method 1, a high-concentration (5.25%) hypochlorite solution was used during the instrumentation of the root canal, and an antibacterial dressing was applied between sessions, followed by filling of the root canal. In method 2, a low-concentration (0.5%) sodium hypochlorite solution was used as an adjunct to mechanical debridement, and the root canal was filled during the same session. The histopathological results showed that method 1 led to better periapical repair than method 2.

Osteomalacia secondary to renal tubular acidosis in a patient with primary Sjögren's syndrome.

We report a case of a 41-year-old woman whose disease manifested as osteomalacia and whose etiological investigation revealed renal tubular acidosis secondary to primary Sjögren's syndrome. Proximal tubular dysfunction was also present and was documented by increased urinary excretion of beta-2-microglobulin and retinol-binding protein. The patient showed clinical and laboratory improvement after treatment with oral potassium citrate, calcium supplements and steroids.