Fenugreek seed extract alleviates hippocampal dendritic atrophy in streptozotocin induced diabetic rats / El extracto de semillas fenugreek alivia la atrofía dendrítica del hipocampo en ratas diabéticas inducidas por estreptozotocina

SUMMARY: Herbal extracts used for treatment of diabetes has focused mostly on the hypoglycaemic and anti-oxidant property.There are no studies which focused on its effect on dendritic architecture of pyramidal neurons of hippocampus caused by diabetes. This study was taken up to explore the effect of administration of Trigonella foenum-graecum (fenugreek) seed extract on diabetes induced dendritic atrophy in hippocampus. Experimental diabetes was induced in rats by administering single dose of Streptozotocin (60 mg/kg)intraperitoneally.Treatment groups of rats were orally administeredfenugreek seed extract of 1 g/kg body weight for 6 weeks. Followingly they were sacrificed and the brains were removed, processed for the Golgi-Cox stain method.The number of dendritic branching points and intersections were counted in successive radial segments of 20 µm up to a radial distance of 100 micron from soma and analysed by the Sholl's method. The rats with diabetes showed a significant decrease in the dendritic length and branching points in most of the apical and basal dendrites of CA1 and CA3 pyramidal neurons.Treatment with fenugreek seed extract were able to significantly alleviate the dendritic atrophy in most of the segments except in the apical branching points of the CA1 neuron. The present study demonstrates that fenugreek seed extract having a proven hypoglycaemic and anti-diabetic property also possess protection to the hippocampal pyramidal neurons form diabetes associated neuronal atrophy.

RESUMEN: Los extractos de hierbas para el tratamiento de la diabetes se han basado principalmente en las propiedades hipoglucémicas y antioxidantes. En la literatura no hay estudios basados en su efecto sobre la arquitectura dendrítica de las neuronas piramidales del hipocampo, causadas por la diabetes. El objetivo de este estudio fue investigar el efecto de la administración de extracto de semilla de Trigonella foenum graecum (fenogreco) sobre la atrofia dendrítica inducida por la diabetes en el hipocampo. Se indujo diabetes experimental en ratas mediante la administración de una dosis única de estreptozotocina (60 mg / kg) por vía intraperitoneal. Se administró a grupos de ratas extracto de semilla de fenogreco a razón de 1 g / kg de peso corporal durante 6 semanas. Las ratas fueron sacrificadas posteriormente y se procesaron los cerebros mediante método de tinción de Golgi-Cox. El número de puntos de ramificación dendrítica e intersecciones se contaron en segmentos radiales sucesivos de 20 µm hasta una distancia radial de 100 micras del soma y se analizaron mediante el método de Sholl. Las ratas con diabetes mostraron una disminución significativa en la longitud dendrítica y los puntos de ramificación en la mayoría de las dendritas apicales y basales de las neuronas piramidales CA1 y CA3. El tratamiento con extracto de semilla de fenogreco alivió significativamente la atrofia dendrítica en la mayoría de los casos, excepto en los puntos de ramificación apical de la neurona CA1. El estudio demuestra que el extracto de semilla de fenogreco además de tener propiedades hipoglucémicas y antidiabéticas, también protege las neuronas piramidales del hipocampo contra la atrofia neuronal asociada a la diabetes.

Efecto de la frecuencia de aplicación de estrógenos locales sobre el grosor endometrial en mujeres posmenopáusicas / Effect of local estrogen application frequency on endometrial thickness in postmenopausal women

Resumen Introducción: Los estrógenos conjugados vía vaginal para aliviar la atrofia y sequedad vaginales pueden producir cambios endometriales. Objetivo: Conocer el efecto de la frecuencia de aplicación de estrógenos conjugados vía vaginal en el grosor endometrial en mujeres posmenopáusicas. Método: Se estudiaron 70 mujeres posmenopáusicas con sequedad vaginal que recibieron estrógenos conjugados en crema (0.625 mg/1 g) durante 12 semanas divididas de la siguiente manera según la frecuencia de aplicación: grupo 1, dos veces por semana (n = 35) y grupo 2, tres veces por semana (n = 35). Al inicio y final del tratamiento se determinó el valor estrogénico en la citología vaginal y se realizó ultrasonido endovaginal para medir el grosor endometrial. La comparación entre los grupos se realizó con U de Mann-Whitney y entre los valores pre y postratamiento con prueba de Wilcoxon. Resultados: De 70 mujeres reclutadas solo se estudiaron 38 mujeres, 19 en cada grupo, pareadas por valor estrogénico inicial. No se encontró diferencia entre los grupos, ni antes ni después del tratamiento, en el índice de maduración, valor estrogénico ni grosor endometrial. Conclusión: No hubo diferencias en el grosor endometrial entre las distintas frecuencias de aplicación de estrógenos conjugados en crema.

Abstract Introduction: Conjugated estrogens, when used by the vaginal route for the relief of vaginal dryness and atrophy, can produce endometrial changes. Objective: To know the effect of vaginal conjugated estrogens application frequency on endometrial thickness in postmenopausal women. Method: Seventy postmenopausal women with vaginal dryness who received conjugated estrogen cream (0.625 mg/1 g) for 12 weeks were studied. The women were divided according to application frequency as follows: group 1, twice-weekly (n = 35), and group 2, thrice-weekly (n = 35). At baseline and at end-of-treatment, vaginal cytology was examined to determine the estrogenic value, and an endovaginal ultrasound was performed to measure endometrial thickness. The comparison between groups was carried out with Mann Whitney's U-test, and the comparison between baseline and post-treatment values, with Wilcoxon's test. Results: Of 70 recruited women, only 38 were studied, 19 in each group, paired by baseline estrogenic value. No difference was found between groups, neither at baseline nor after treatment, in the maturation index, estrogenic value or endometrial thickness. Conclusion: There were no differences in endometrial thickness between the conjugate estrogen cream different application frequencies.

Subclinical atherogenesis in patients with mild psoriasis: A role for IL-6? / Aterogênese subclínica em pacientes com psoríase leve: um papel para IL-6?

Summary Introduction: A link of psoriasis with subclinical atherosclerosis has been postulated and cytokine network might intermediate this association. Few data are available in patients with mild psoriasis. We evaluated carotid intima-media thickness (cIMT) in drug-free psoriatic individuals and controls. In parallel, we searched for associations of cIMT with disease activity indexes and serum interleukins (IL) in psoriatic patients. Method: An experienced radiologist performed the cIMT analyses. Cytokine concentrations were assessed by flow cytometry. Disease activity was evaluated based on psoriasis area and severity index (PASI) as well as body surface area (BSA). Results: Sixty-five (65) patients and 64 controls were studied. Mean age of patients (50.9 years) did not differ from controls (p=0.362). A low PASI and BSA (< 10) prevailed (69.2% and 56.9%, respectively). Median levels of IL-12p70, TNF-α, IL-1β and IL-10 were significantly lower in cases than in controls (adjusted p<0.05), while IL-6 and IL-8 medians did not differ between groups (adjusted p>0.05). Smoking habit and diabetes mellitus predominated in cases (p=0.002). An altered cIMT (≥ 0.9 mm) was more frequent in cases than in controls (23.8% versus 8.5%, adjusted p=0.045). Mean cIMT was higher in cases with a borderline significance (p=0.057). cIMT scores did not correlate to PASI (rs=0.066; p=0.250) or BSA (rs=0.175; p=0.185), but did correlate significantly with serum IL-6 (rs=0.26; p=0.005). Conclusion: Subclinical atherosclerosis was more frequent in patients with mild psoriasis than controls. cIMT in psoriatic individuals correlated with serum IL-6, pointing to an eventual proatherogenic role of IL-6 in these patients. Newer studies should clarify the connection of atherogenesis with cytokines in psoriasis.

Resumo Introdução: Foi postulada uma ligação entre psoríase e aterosclerose subclínica. A rede de citocinas pode intermediar essa associação. Poucos dados estão disponíveis em pacientes com psoríase leve. Avaliamos a espessura íntima-média carotídea (cIMT) em psoriáticos e controles livres de medicação. Paralelamente, pesquisamos a associação de cIMT com os índices de atividade de doença e interleucinas séricas (IL) em pacientes com psoríase. Método: Um radiologista experiente procedeu à análise do cIMT. As concentrações de citocinas foram avaliadas por citometria de fluxo. A atividade da doença foi avaliada pelo índice de gravidade (PASI) e pela área de superfície corporal (BSA). Resultados: Sessenta e cinco (65) pacientes e 64 controles foram estudados. A idade média dos pacientes (50,9 anos) não diferiu dos controles (p=0,362). PASI e BSA baixos (< 10) prevaleceram (69,2% e 56,9%, respectivamente). As medianas de IL-12p70, TNF-α, IL-1β e IL-10 foram significativamente menores nos casos do que nos controles (p<0,05 ajustado), enquanto as medianas de IL-6 e IL-8 não diferiram nos grupos (p>0,05 ajustado). Tabagismo e diabetes mellitus predominaram nos casos (p=0,002). Um cIMT alterado (≥ 0,9 mm) foi mais frequente nos casos do que nos controles (23,8% versus 8,5%, p=0,045 ajustado). A média de cIMT foi maior nos casos com significância borderline (p=0,057). Os escores de cIMT não se correlacionaram com o PASI (rs=0,066; p=0,250) ou o BSA (rs=0,175; p=0,185), mas se correlacionaram significativamente com a IL-6 sérica (rs=0,26; p=0,005). Conclusão: A aterosclerose subclínica foi mais frequente em pacientes com psoríase leve do que nos controles. Em psoriáticos, cIMT correlacionou-se com níveis de IL-6 no soro, apontando para um eventual papel pró-aterogênico para a IL-6 nesses pacientes. Novos estudos devem esclarecer a ligação da aterogênese com citocinas na psoríase.

Effect of a gel containing pilocarpine on vaginal atrophy in castrated rats

OBJECTIVES: To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats. METHODS: Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non-parametric test with a weighted linear regression model was used for data analysis (p<0.05). RESULTS: The morphological evaluation showed maturation of the vaginal epithelium with keratinization in Group I, whereas signs of vaginal atrophy were present in the rats of the other groups. Morphometric examinations showed mean thickness values of the vaginal epithelium of 195.10±12.23 μm, 30.90±1.14 μm, 28.16±2.98 μm and 29.84±2.30 μm in Groups I, II, III and IV, respectively, with statistically significant differences between Group I and the other three groups (p<0.0001) and no differences between Groups II, III and IV (p=0.0809). CONCLUSION: Topical gel formulations containing pilocarpine had no effect on atrophy of the vaginal epithelium in the castrated female rats.

Atrofia urogenital: seguridad del tratamiento con estrógenos vaginales / Safety of vaginal estrogens for urogenital atrophy

Urogenital atrophy is characterized by dryness, inflammation, and thinning of the epithelial lining of the vagina and lower urinary tract due to estrogen decline. Local estrogen therapy if effective to relieve signs and symptoms of vaginal atrophy without causing an elevation of serum estrogen levels. Although there are no big studies addressing the safety of this type of treatment, it can be maintained over long periods to avoid annoying symptoms. Special care must be taken with women with breast cancer in whom the effective dose must be titrated to avoid an increase in serum estrogens over the levels usually observed in postmenopausal women.

Promestrieno no tratamento da atrofia vulvovaginal: revisão sistemática / Promestriene for treatment of vulvovaginal atrophy: a systematic review

Os sintomas decorrentes da atrofia vulvovaginal são muito comuns no climatério. Os estrogênios aplicados localmente na vagina se mostram eficazes no alívio de tais manifestações; no entanto, os estrogênios conjugados na forma de creme vaginal apresentam efeitos sistêmicos e o estriol aplicado localmente pode ser absorvido sistemicamente também. O promestrieno é um estrogênio cuja absorção sistêmica é desprezível quando empregado topicamente, porém a falta de revisão sistemática sobre o tema suscitou a realização da presente revisão. Foram incluídos 16 estudos publicados entre 1976 e 2009, que avaliaram eficácia do promestrieno no alívio dos sintomas decorrentes da atrofia vulvovaginal, ou que investigaram seus efeitos na citologia vaginal, e também aqueles que avaliaram a absorção da substância quando empregada topicamente. As evidências encontradas confirmaram a eficácia do promestrieno, utilizado localmente no tratamento das afecções atróficas genitais femininas decorrentes do hipoestrogenismo, aliada a absorção sistêmica desprezível

The symptoms resulting from vulvovaginal atrophy are very common during climacteric. Estrogens applied locally in the vagina are effective in relieving these manifestations, however, conjugated estrogens as vaginal cream have systemic effects and locally applied estriol may be systemically absorbed. Promestriene is an estrogen without systemic absorption when applied topically, but the lack of a systematic review on the substance motivated the idea to make this review. Sixteen studies published between 1976 and 2009 which evaluated the effectiveness of promestriene on the relief of symptoms resulting from vulvovaginal atrophy or which investigated its effects on vaginal cytology and those which evaluated the absorption of the substance when used locally were included. The found evidences confirmed the effectiveness of locally applied promestriene in the treatment of female genital atrophic disorders due to low estrogen levels coupled with negligible systemic absorption

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy.

Tratamento prolongado da vaginite atrófica pelo promestriene: resultados e tolerância / Prolonged treatment of athrophic vaginitis with promestriene: results and tolerance

Vinte pacientes menopausadas portadoras de vaginite atrófica com ausência de células superficiais ao esfregaço cito-hormonal foram tratadas durante quatro a seis meses, através de terapias mensais de 20 dias, com cápsulas vaginais de promestriene. O tratamento proporcionou modificaçäo significativa da citologia vaginal, que consistiu principalmente no desenvolvimento das células intermediárias às custas das células basais. Näo houve elevaçäo da taxa plasmática do estradiol e näo foi observada qualquer modificaçäo nos parâmetros clínicos e biológicos examinados. Tais conclusöes foram estatisticamente significativas. O estudo confirmou também a boa tolerância do promestriene administrado em tratamentos prolongados e/ou repetidos, freqüentemente necessários nas pacientes menopausadas.

Uso do promestriene por via vaginal: avaliaçäo da colpocitologia hormonal, dos níveis plasmáticos de gonadotrofinas e estradiol em mulheres na menopausa: análise da eficácia e tolerabilidade / Use of promestrien by intravaginal route: evaluation of hormonal colpocytology, plasma levels of gonadotrophins and estradiol in menopausal women: analysis of effectiveness and tolerability

Os autores estudaram os efeitos da administraçäo do promestriene por via vaginal em mulheres na pós-menopausa. Um grupo de 14 pacientes recebeu a droga em regime de administraçäo diária, contínua, por 60 dias. Um segundo grupo, com 16 pacientes, foi tratado em regime de administraçäo diária, contínua, por 20 dias e, a seguir, três vezes por semana por mais 40 dias. Analisaram a evoluçäo da colpocitologia hormonal e dos níveis de gonadotrofinas, bem como a tolerabilidade e eficácia da medicaçao ao longo do estudo. Concluem ser o promestriene um agente antiatrófico vaginal efetivo, sem produzir alteraçöes dos níveis plasmáticos de gonadotrofinas e estradiol. Nao observaram diferenças estatísticas nos dois regimes de administraçäo estudados.