Impact of topical nifedipine on wound healing in animal model (pig) / Impacto da nifedipina tópica na cicatrização de feridas em modelo animal (porco)

Abstract Background The human skin is an extremely sophisticated and evolved organ that covers the whole body. External agents or the patient's own diseases can cause skin injuries that can challenge healthcare professionals and impose high social, economic and emotional costs. Objectives To evaluate the impact of topical nifedipine on skin wound healing, specifically on polymorphonuclear cells, vascular proliferation, and collagen. Methods We used three pigs, and created eight injuries in the dorsal region of each animal. We applied 1%, 10%, and 20% concentration nifedipine creams to four of the wounds in animals 1, 2, and 3 respectively and treated the other twelve wounds with saline solution 0.9% only. We analyzed the presence of polymorphonuclear cells, vascular proliferation, and collagen at six different times (days 1, 3, 7, 14, 21, and 28). Results The evaluation of polymorphonuclear levels showed mild cell activity at all times in the control group, while in the nifedipine groups, marked levels were more frequent at all times during the experiment. There was a 4.84-fold increase in the chance of marked vascular proliferation (p = 0.019) and, at the same time, a decrease in collagen formation (OR 0.02 / p = 0.005) in animal 3. Conclusions Topical NFD may have an impact on skin wound healing mechanisms. Our study showed that polymorphonuclear cells and vascular proliferation increased. We also demonstrated that collagen formation decreased. Therefore, topical NFD may have a positive impact on skin wound healing. Additional studies are needed to confirm our results.

Resumo Contexto A pele humana é um órgão extremamente sofisticado e evoluído que cobre todo o corpo. As lesões cutâneas podem ser causadas por agentes externos ou pelas próprias doenças do paciente, e podem representar um desafio para os profissionais de saúde com altos custos sociais, econômicos e emocionais. Objetivos Avaliar o impacto da nifedipina tópica na cicatrização de feridas cutâneas, especialmente em relação a polimorfonucleares, proliferação vascular e colágeno. Métodos Utilizamos três porcos e realizamos oito ferimentos na região dorsal de cada animal. Aplicamos as concentrações de nifedipina creme a 1%, 10% e 20% para os animais 1, 2 e 3, respectivamente, sendo que, em quatro ferimentos, aplicamos o creme e, nos outros quatro ferimentos, apenas soro fisiológico a 0,9%. Analisamos a presença de polimorfonucleares, proliferação vascular e colágeno em seis momentos diferentes (dias 1, 3, 7, 14, 21 e 28). Resultados A avaliação dos níveis polimorfonucleares mostrou atividade celular discreta em todos os momentos no grupo controle, enquanto nos grupos nifedipina, os níveis marcados foram mais frequentes em todos os momentos do experimento. Houve aumento de 4,84 vezes na chance de uma produção marcada (p = 0,019) da proliferação vascular e, ao mesmo tempo, diminuição da formação do colágeno (odds ratio, OR 0,02; p = 0,005) no animal 3. Conclusões A nifedipina tópica pode ter impacto no mecanismo de cicatrização cutânea. Nosso estudo mostrou que há aumento dos polimorfonucleares e da proliferação vascular. Além disso, há diminuição da formação do colágeno. Assim, a nifedipina tópica pode ter impacto positivo na cicatrização das feridas cutâneas. Estudos adicionais são necessários para confirmar nossos resultados.

Prevalência de alta reatividade plaquetária em pacientes tratados com aspirina encaminhados para angiografia coronária / Prevalence of high platelet reactivity in aspirin-treated patients referred for coronary angiography

FUNDAMENTO: A aspirina (Ácido Acetilsalicílico - AAS) é capaz de reduzir eventos adversos cardiovasculares em pacientes portadores de Doença Arterial Coronariana (DAC) através da inibição da atividade plaquetária. Alguns pacientes com DAC, apesar da terapia com AAS, apresentam Alta Reatividade Plaquetária (ARP), o que determina um maior risco para o desenvolvimento de eventos cardiovasculares. OBJETIVO: O objetivo deste estudo foi determinar a prevalência de ARP em pacientes tratados com AAS e encaminhados para cinecoronariografia, além de avaliar se existe uma possível correlação entre a gravidade da DAC e o desenvolvimento de ARP. MÉTODOS: Estudo de centro único onde foram incluídos 115 pacientes consecutivos, tratados com AAS e portadores de DAC estável. A reatividade plaquetária induzida pelo ADP e colágeno foram avaliadas através da Agregometria de Transmitância Luminosa (ATL). Pacientes com agregação plaquetária maior que 70%, induzida por ambos os reagentes, foram classificados como tendo ARP e, neste grupo, a adesão ao tratamento com AAS foi avaliada através da dosagem dos níveis séricos de salicilato. RESULTADOS: A média de idade foi de 60,9 anos e a dose média de AAS foi de 164,2 mg. Tabagismo e diabetes melito estavam presentes em 28,7% e 31,5% dos pacientes, respectivamente. Foi encontrada ARP em 14 pacientes (13%), entretanto, em sete indivíduos (50%) com ARP observaram-se baixos níveis séricos de salicilato (< 2,0 µg/mL), sugerindo não adesão à terapia medicamentosa. Em 6,5% dos pacientes com ARP identificou-se níveis detectáveis de salicilato sérico, sugerindo uma eficácia reduzida do AAS. A ARP se correlacionou com o número e a gravidade das estenoses coronárias (p = 0,04). CONCLUSÃO: Em uma população de pacientes tratados com AAS e encaminhados para angiografia coronária, a reatividade plaquetária elevada é prevalente (13%), sendo 50% destes pacientes não aderentes à terapia farmacológica e 50% apresentam redução da efetividade da droga.

BACKGROUND: Aspirin (ASA) reduces adverse events in coronary artery disease (CAD) patients by inhibiting platelets. Some CAD patients have high platelet reactivity (HPR) despite ASA therapy and these individuals have increased risk of adverse events. OBJECTIVE: The purpose of this study was to determine the prevalence of HPR in ASA-treated patients referred for coronary angiography and to assess whether the HPR correlates with the severity of CAD. METHODS: This single center investigation enrolled 115 consecutive ASA-treated patients with stable CAD. ADP- and collagen-induced platelet reactivity were evaluated by light transmittance aggregometry (LTA). Patients with greater than 70% ADP- and collagen-induced aggregation were determined to have HPR and, in this group, ASA compliance was assessed by examining blood salicylate levels. Mean age was 60.9 years and average ASA dose was 164.2 mg. RESULTS: Smoking and DM were present in 28.7% and 31.5% respectively. HPR was found in 14 patients (13%) however 7 of the 14 patients (50%) with HPR had low serum salicylate levels (< 2.0 µg/mL) suggesting medication noncompliance. Of the entire cohort, 6.5% of patients had HPR and detectable serum salicylate levels suggesting reduced ASA efficacy. HPR correlated with number and severity of coronary stenosis (p = 0.04). CONCLUSION: In a general population of ASA-treated patients referred for coronary angiography, elevated platelet reactivity is prevalent (13%) with 50% related to noncompliance and 50% related to reduced aspirin efficacy.

Telopeptido carboxilo terminal del colageno tipo i ( beta-ctx ) serico y / compromiso oseo en la insuficiencia renal cronica / Serum beta-type I collagen carboxyterminal telopeptide ( beta-CTXs ) and bone involvement in chronic renal failure

La osteodistrofia renal (ODR) se caracteriza por alteraciones óseas. Se evaluaron métodos bioquímicosalternativos a la biopsia ósea en pacientes renales para determinar cambios rápidos delremodelamiento óseo en 43 pacientes predialíticos (PD) y 49 hemodializados (HD). Los PD presentaronfosfatemia, fosfatasa alcalina ósea (FAO), hormona paratiroidea intacta (PTHi) y beta-telopéptido carboxilo terminaldel colágeno tipo I (betaCTXs) mayores y clearence de creatinina (Ccr) menores (p<0.001) que los controles.La fosfatemia de HD fue más elevada, significativamente respecto de controles (p<0.0001); FAO, PTHi y betaCTXsfueron mayores a los otros dos grupos (p<0.0001). En ambos grupos renales betaCTXs y FAO correlacionaroncon PTHi (p<0.002 y p<0.0001, respectivamente) y entre sí (p<0.0001). Los PD con Ccr <40 ml/min presentaronPTHi, FAO y bCTXs (p<0.004, p<0.05 y p<0.001, respectivamente) más elevados que aquellos con Ccr>40ml/min. En PD, betaCTXs (p<0.05) y en HD tanto betaCTXs como FAO (p<0.0001) estaban aumentados respecto decontroles, aun con PTHi normal. Los incrementos mayores en los marcadores óseos se observaron en los pacientescon mayores niveles de PTHi (p<0.001). En conclusión; aun sin PTHi elevada existe un aumento deresorción ósea (posiblemente por otros factores) y la medición de betaCTXs sería una herramienta apropiada notraumática para detectar tempranamente alteraciones óseas por IR que permitiría tomar medidas preventivaspara evitar dicha pérdida. Asimismo, instalada la ODR determinar el aumento del remodelamiento sería sumamenteútil para identificar pacientes que requieran biopsia ósea. El reemplazo de la misma por beta-CTX séricodeberá esperar estudios que demuestren la correlación existente entre ambas metodologías.

Serum levels of aminoterminal propeptides of type I collagen indicating osteoporsis in early postmenopausal women with correlation to bone densitometry

To reduce accelerated bone loss in early postmenopause and to minimize the risk of fracture, a variety of antiresorptive treatments [e.g. calcium, calcitonin, estrogen and bisphosphonates] was used. Among the different bone resorption markers, degradation products of type I collagen have demonstrated their superiority. The serum levels of aminoterminal propeptides [PINP] of type I collagen were determined in the sera of 60 healthy postmenopausal women subjected to densitometric measurements of lumber vertebrae to indicate osteoporosis. Bone mineral densitometry [BMD] was most strongly associated with the serum levels of propeptides type I collagen. The value of PINP may be used as an indicator not only for the treatment evaluation but also as a predictor of the risk of occurrence of hip or spine bone fractures

The Skeletal Site-Differential Changes in Bone Mineral Density Following Bone Marrow Transplantation: 3-Year Prospective Study

Loss of bone mass is usually detected after bone marrow transplantation (BMT) during the early post-transplant period. However, little is known about the long-term effects of BMT on bone metabolism. We have prospectively investigated 11 patients undergoing BMT. Bone mineral density (BMD) was measured before BMT, and 1, 2, and 3 yr after BMT. Serum markers of bone turnover were serially measured before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 yr after BMT. The mean change in the lumbar spine (L2-4) BMD, calculated as the percent change from the baseline to the level at 1, 2, and 3 yr was -4.7% (NS), -1.1% (NS), and +6.4% (p<0.05), respectively. The mean change in the total proximal femur BMD from the baseline to the level at 1, 2, and 3 yr was -8.5% (p<0.01), -8.7% (p<0.05) and -5.6% (p<0.05), respectively. In summary, there was little decline in lumbar BMD at 1 yr following BMT and gradual recovery until 3 yr. In contrast, femoral BMD decreased much more than the lumbar area at 1 yr and did not recover until 3 yr. The mechanism of skeletal site-selective differences in the changes of BMD needs to be elucidated.

Study of the level of biochemical bone markers: NMID osteocalcin and bone resorptive marker (beta CTx) in Thai women.

Study of the level of NMID osteocalcin and Beta CTx in 700 Thai women. The mean of NMID osteocalcin = 21.45 SD = 11.18 95% CI = 20.12 to 22.79 ng/ml and betacrosslap = 0.445 ng/ml SD = 0.25 with 95% CI = 0.414 to 0.478 ng/ml in women who menopaused less than 10 years ago (n=237), these values were higher than in young adult females (n=63) and menstruating women (n=123) which was statistically significant (p=0.0001). The value of both bone markers in elderly women who had menopaused more than 10 years ago and were aged more than 60 years (n=94) showed a marked increase of NMID osteocalcin, 25.63 ng/ml SD = 14.22 ng/ml but the value of betacrosslap was below the young-menopausal women, 0.394 ng/ml SD = 0.241 ng/ml 95% CI = 0.344 to 0.444 ng/ml. Menopausal women are at a high risk of osteoporosis due to high bone turnover. In our study, the NMID osteocalcin had a high correlation with betacrosslap (r=0.789 p=0.0001) while both bone markers had a weak correlation with bone mass density of radius, lumbar spine and hip by DXA. (r=0.29 p=0.0001).

The parathyroid hormone level in Thai women.

Study of the correlation of parathyroid hormone (PTH) with age, radial bone mass and Nitrogenous mid fragment osteocalcin (NMID osteocalcin) in 226 menopausal women and 123 menstrual women. In menopausal women, aged between 50 and 69, the level of PTH did not increase with age (r=0.001, p=NS). Elderly women (n=123, age>70) showed a slight increase of PTH, 7.8 per cent compared to menstruating women. In elderly women (n=100, age>60) there was no weak correlation (r=0.11, p=0.0001) with bone mass of the distal end of the radius measured by Dual X-ray Absorptiometry (DXA) (Panasonic BDM-3) and no correlation between PTH and the resorptive bone marker, (betacrosslap) (r=0.11, n=122).

Serum dehydroepiandrosterone sulfate, testosterone, and biochemical markers of bone turnover in elderly Thai men.

The most abundant human steroid, dehydroepiandrosterone sulfate (DHEAS), may have a multitude of beneficial effects, but declines with age. It is unclear whether DHEAS deficiency is an important factor contributing to increased bone resorption and impaired bone formation or not that leads to their bone loss. Thus, we investigated serum DHEAS, testosterone, osteocalcin (N-MID osteocalcin) and C-terminal telopeptides (beta-CrossLaps) in 121 healthy Thai males without bone diseases. Thirty-nine males (mean age 31.5 +/- 8.2, range 23-42 years) were recruited as the normal adult group and 82 males (mean age 61.2 +/- 7.0, range 52-77 years) were assigned as the elderly group. DHEAS levels were higher in the adult group compared with the elderly subjects (296.8 +/- 93.4 vs 172.6 +/- 99.8 microg/dL, p < 0.0001). Serum osteocalcin concentrations were also higher in the adult group compared with the elderly males (27.9 +/- 11.1 vs 23.2 +/- 7.9 ng/ml, p = 0.0091). However, serum testosterone and C-terminal telopeptides levels were not significantly different between the two groups. We concluded that low DHEAS concentrations are commonly encountered in elderly males and may relate to low osteocalcin levels due to the osteoblast stimulation effects of DHEAS. These findings may be implicated in the treatment of osteoporosis in elderly men by using DHEAS.

Utilidad clínica de los marcadores de formación y resorción ósea / Clinical utility of biochemical merkers of bone turnover

Se evaluó el recambio óseo en distintas situaciones fisiológicas y patológicas que alteran el metabolismo óseo. A tal fin se analizó la utilidad de un marcador bioquímico de formación como la fosfatasa alcalina ósea (FAO) y uno de resorción ósea, como la fracción carboxilo terminal del telopéptido del colágeno tipo I (CTX). En la población adulta normal los hombres y mujeres premenopáusicas no presentaron diferencias significativas. Contrariamente, las mujeres posmenopáusicas tuvieron niveles de FAO y CTX significativamente mayores que éstos dos grupos (p<0,01). Entre el segundo y tercer trimestre de embarazo ambos marcadores aumentaron significativamente (FAO: p<0,009 y CTX: p<0,0003). Mientras la FAO no varió en posmenopáusicas ante el tratamiento hormonal de reemplazo (THR), el CTX disminuyó significativamente (p<0,001). Mujeres posmenopáusicas osteopénicas y osteoporóticas presentaron niveles de CTX y FAO significativamente menores luego de THR o tratamiento con bifosfonatos respecto de las no tratadas (FAO: p<0,05 y 0,03 y CTX: p<0,02 y 0,0001 respectivamente). Pacientes con insuficiencia renal en hemodiálisis presentaron niveles séricos de FAO y CTX significativamente mayores que los controles sanos por edad y sexo (p<0,05). Pacientes hipertiroideos, pagéticos o con patología ósea secundaria a enfermedad celíaca disminuyeron los niveles de FAO y CTX en forma significativa (p<0,05) luego del tratamiento específico. Como se esperaba, el marcador de resorción respondió más rápidamente a cambios en el remodelamiento óseo. Si le sumamos la alta especificidad y sensibilidad del CTX, se sugiere que éste marcador sería de utilidad en todas aquellas patologías en que se sospeche alteración o se quiera determinar el grado del remodelamiento óseo

Sensibilidad de los marcadores del remodelamiento óseo: su modificación en la menopausia, ante la terapia estrogénica de reemplazo y ante una enfermedad metabólica generalizada / Markers of bone turnover, their sensibility to bone remodeling: changes in menopause, in hormone replacement therapy and in a metabolic bone disease

Evalua una batería de marcadores bioquímicos específicos y sensibles para predecir cambios en la velocidad del remodelamiento óseo. Se estudió a mujeres sanas pre y postmenospáusicas y en estas últimas a su vez se evaluó los cambios producidos después de 90 días de una terapia hormonal de reemplazo. Respecto de los marcadores bioquímicos de formación, la FA total aumentó en las postmenospáusicas respecto del grupo premenospáusico (P < 0,0001), al igual que la BGP (1 < 0,01); en cambio, la FA ósea no registró cambios significativos. Luego de la terapia hormonal de reemplazo ninguno de estos marcadores registraron cambios significativos. Todos los marcadores de resorción aumentaron en als mujeres postmenospáusicas. Los convencionales tales como el calcio urinario/creatinina y la hidroxiprolina con un p < 0,01 y p < 0,006 respectivamente. Los nuevos marcadores de resorción presentaron los siguientes cambios: Pyr p < 0,001; 72 por ciento; D-Pyr p < 0,003, 27 por ciento y Crosslaps p < 0,003, 70 por ciento de aumento respectivamente. Ante la terapia estrogénica, si bien los marcadores convencionales no mostraron diferencias significativas respecto del nivel basal, la Pyr disminuyó significativamente en un 15 por ciento (p < 0,03), la D-Pyr en un 15 por ciento (p < 0,04) y los Crosslaps en un 39 por ciento (p < 0,001). También se investigó la precisión diagnóstica de los marcadores bioquímicos en pacientes con un remodelamiento óseo aumentado, como es el caso de enfermedades celíacas. Estas se compararon con los normales que presentaban igual estado estrogénico observándose distintos comportamientos entre pre y postmenospáusicas. La BGP aumentó sólo en las celíacas premenospáusicas (p < 0,003). La FA total en los dos grupos estrogénicos (p < 0,0001 y p < 0,005 respectivamente), al igual que la FA ósea (p < 0,0003 y p< 0,0004, respectivamente). El marcador de resorción D-Pyr no presentó diferencias significativas en ninguno de los dos grupos, la Pyr sílo en las premenopáusicas (p < 0,01). La hidroxiprolina aumentó en ambos (p < 0,04 y p < 0,004, respectivamente), al igual que los Crosslaps (p < 0,001 para los dos grupos estrogénicos)

Serum type IV collagen concentrations in patients with longstanding essential hypertension

Relation between LS EHT and type IV serum collagen concentration was estimated by RIA. The ACV was estimated from CXR, PA view and it lateral view with barium and RCV was deduced. Twenty-two patients with LS EHT were chosen. Ten normal persons were taken as a control group. Serum collagen concentration and RCV were found to be significantly high in the patients group [P <0.01 and P <0.05, respectively]. A positive correlation was found between serum collagen concentration and RCV [r = 0.97] and another positive correlation was also found between DBP and serum collagen concentration [r = 0.74]. It was concluded that LS EHT has an effect on the capillary basement membrane. It may increase the synthesis, the deposition and the turn over the type IV serum collagen. Serum type IV collagen concentration is a useful noninvasive marker for the activity and progression of hypertension

Plasma type IV collagen and fibronectin concentrations in diabetic patients with microangiopathy

In diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. We evaluated whether the plasma levels of type IV collagen and fibronectin, which are important factors of basement membrane, are related with the presence of diabetic microangiopathy. Plasma type IV collagen and fibronectin levels were measured in 40 healthy controls (Mean +/- SD, age; 50.3 +/- 5.5 yr) and 94 diabetic patients (age; 52.4 +/- 13.5 yr) with and without microvascular complications. The mean plasma levels of type IV collagen (5.3 +/- 2.9 ng/ml) and fibronectin (474.4 +/- 119.4 ug/ml) in diabetic patients were significantly higher (p < 0.01) than in healthy controls (3.7 +/- 1.3 ng/ml and 319 +/- 50.9 ug/ml). The mean plasma level of type IV collagen in diabetic patients with complications (6.6 +/- 3.7 ng/ml) was significantly higher (p < 0.01) than in those without complications (4.3 +/- 1.7 ng/ml) and became higher in more complicated patients. Furthermore, the severity of retinopathy and several indicators of nephropathy such as serum BUN, creatinine and proteinuria were closely associated with plasma type IV collagen level and a significant correlation was found between plasma type IV collagen and creatinine clearance (r = -0.31, p < 0.001). There was no significant difference in plasma fibronectin concentrations, however, between the diabetic patients with complications and those without complications.(ABSTRACT TRUNCATED AT 250 WORDS)