Pathogenesis, Assessment, and Treatment of Coronary Microcirculation Dysfunction. / Patogênese, Avaliação e Tratamento da Disfunção da Microcirculação Coronariana.

Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

A doença cardiovascular é a causa predominante de mortalidade em escala global. A pesquisa indica que as mulheres, em comparação aos homens, apresentam maior probabilidade de apresentar doença arterial coronariana (DAC) não obstrutiva quando têm sintomas de isquemia miocárdica. Além disso, as mulheres tendem a apresentar uma maior carga de sintomas em relação aos homens e, apesar da presença de doença cardíaca isquêmica, são frequentemente tranquilizadas erroneamente devido à ausência de DAC obstrutiva. Nos casos de cardiopatia isquêmica acompanhada de sintomas de isquemia miocárdica, mas sem DAC obstrutiva, é imperativo considerar a disfunção microvascular coronariana como uma potencial causa subjacente. A disfunção microvascular coronariana, caracterizada por reserva de fluxo coronariano prejudicada resultante de anormalidades funcionais e/ou estruturais na microcirculação, está associada a desfechos cardiovasculares adversos. Modificações no estilo de vida e o uso de medicamentos antiateroscleróticos e antianginosos podem oferecer benefícios potenciais, embora sejam necessários mais ensaios clínicos para informar estratégias de tratamento. Esta revisão tem como objetivo explorar a prevalência, mecanismos subjacentes, abordagens diagnósticas e intervenções terapêuticas para disfunção microvascular coronariana.

Patogênese, Avaliação e Tratamento da Disfunção da Microcirculação Coronariana / Pathogenesis, Assessment, and Treatment of Coronary Microcirculation Dysfunction

Resumo A doença cardiovascular é a causa predominante de mortalidade em escala global. A pesquisa indica que as mulheres, em comparação aos homens, apresentam maior probabilidade de apresentar doença arterial coronariana (DAC) não obstrutiva quando têm sintomas de isquemia miocárdica. Além disso, as mulheres tendem a apresentar uma maior carga de sintomas em relação aos homens e, apesar da presença de doença cardíaca isquêmica, são frequentemente tranquilizadas erroneamente devido à ausência de DAC obstrutiva. Nos casos de cardiopatia isquêmica acompanhada de sintomas de isquemia miocárdica, mas sem DAC obstrutiva, é imperativo considerar a disfunção microvascular coronariana como uma potencial causa subjacente. A disfunção microvascular coronariana, caracterizada por reserva de fluxo coronariano prejudicada resultante de anormalidades funcionais e/ou estruturais na microcirculação, está associada a desfechos cardiovasculares adversos. Modificações no estilo de vida e o uso de medicamentos antiateroscleróticos e antianginosos podem oferecer benefícios potenciais, embora sejam necessários mais ensaios clínicos para informar estratégias de tratamento. Esta revisão tem como objetivo explorar a prevalência, mecanismos subjacentes, abordagens diagnósticas e intervenções terapêuticas para disfunção microvascular coronariana.

Abstract Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

Immune infiltration could predict the efficacy of short-term radiotherapy in patients with cervical cancer.

Radiotherapy is the main treatment for cervical cancer. It is usually applied alone or in combination with surgery and/or chemotherapy. To explore the association between immune microenvironment of cervical cancer and radiotherapy response, we collected 20 paired cervical cancer tumor samples before and after radiotherapy and partial clinical information. With paired-end RNA-seq, we quantified the immune infiltration and tumor purity of these samples, and obtained 6350 differentially expressed genes before and after radiotherapy. With the help of R language, the function enrichment analysis and 22 immune cells infiltration analysis were carried out. Moreover, we built a random forest model based on the immune microenvironment to predict the short-term efficacy of radiotherapy. We found that the effect of radiotherapy on the immune microenvironment of stage III and IV cervical cancer patients was weaker than that of stage I and II cervical cancer patients. Radiotherapy can significantly reduce the tumor purity and increase immune infiltration. The proportions of the immune infiltrating cells are predictive of the radiotherapy efficacy. In addition, the local mucositis caused by radiotherapy can improve the curative effect of radiotherapy.

Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain.

Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.

Speciation, bioaccessibility and potential risk of chromium in Amazon forest soils.

Even though the Amazon region is widely studied, there is still a gap regarding Cr exposure and its risk to human health. The objectives of this study were to 1) determine Cr concentrations in seven chemical fractions and 6 particle sizes in Amazon soils, 2) quantify hexavalent Cr (CrVI) concentrations using an alkaline extraction, 3) determine the oral and lung bioaccessible Cr, and 4) assess Cr exposure risks based on total and bioaccessible Cr in soils. The total Cr in both A (0-20 cm) and B (80-100 cm) horizons was high at 2346 and 1864 mg kg-1. However, sequential extraction indicated that available Cr fraction was low compared to total Cr, with Cr in the residual fraction being the highest (74-76%). There was little difference in total Cr concentrations among particle sizes. Hexavalent Cr concentration was also low, averaging 0.72 and 2.05 mg kg-1 in A and B horizon. In addition, both gastrointestinal (21-22 mg kg-1) and lung (0.95-1.25 mg kg-1) bioaccessible Cr were low (<1.2%). The low bioavailability of soil Cr and its uniform distribution in different particle sizes indicated that Cr was probably of geogenic origin. Exposure based on total Cr resulted in daily intake > the oral reference dose for children, but not when using CrVI or bioaccessible Cr. The data indicated that it is important to consider both Cr speciation and bioaccessibility when evaluating risk from Cr in Amazon soils.

Repellent activity of essential oils extracted from five Artemisia species against Tribolium castaneum (Coleoptera: Tenebrionidae) / Actividad repelente de aceites esenciales extraídos de cinco especies de Artemisia contra Tribolium castaneum (Coleoptera: Tenebrionidae)

Artemisia genus (family Asteraceae) has been widely used as medicines and cosmetic. The chemical compositions of essential oils extracted from five Artemisia species (A. anethoides, A. giraldii, A. roxburghiana, A. rubripes and A. sacrorum) were analyzed and the repellent activities of five essential oils were investigated by testing percent repellency (PR) in petri dish against Tribolium castaneum. By GC-MS analysis, the common components of the five essential oils were eucalyptol (11.09%-50.05%), camphor (6.28%-33.10%), terpinen- 4-ol (2.46%-12.41%), ß-caryophyllene (0.63%-10.68%) and germacrene D (2.28%-10.01%). 3,3,6-trimethyl-1,4-heptadien-6-ol (11.72%), 2-isopropyl-5-methyl-3-cyclohexen-1-one (24.80%) and ß-farnesene (12.23%) were the characteristic compounds in essential oils of A. sacrorum, A. anethoides and A. rubripes respectively. The essential oils of five plants showed repellent activity against T. castaneum. The PR of others four essential oils were comparable with DEET expect for A. sacrorum. The results indicated that the essential oils of A. anethoides, A. giraldii, A. roxburghiana and A. rubripes had the potential to be developed as repellent for control of T. castaneum.

El género Artemisia (familia Asteraceae) ha sido ampliamente utilizado como medicamentos y cosméticos. Se analizaron las composiciones químicas de los aceites esenciales extraídos de cinco especies de Artemisia (A. anethoides, A. giraldii, A. roxburghiana, A. rubripes y A. sacrorum) y se investigaron las actividades repelentes de cinco aceites esenciales mediante la prueba de repelencia porcentual (PR) en placa de petri contra Tribolium castaneum. Por análisis GC-MS, los componentes comunes de los cinco aceites esenciales fueron eucaliptol (11,09% -50,05%), alcanfor (6,28% -33,10%), terpinen-4-ol (2,46% -12,41%), ß-cariofileno 0,63% -10,68%) y germacrén D (2,28% -10,01%). 3,3,6-trimetil-1,4-heptadien-6-ol (11,72%), 2-isopropil-5-metil-3-ciclohexen-1-ona (24,80%) y ß-farneseno (12,23%). Los compuestos característicos en los aceites esenciales de A. sacrorum, A. anethoides y A. rubripes respectivamente. Los aceites esenciales de cinco plantas mostraron actividad repelente contra T. castaneum. El PR de otros cuatro aceites esenciales eran comparables con DEET esperado para A. sacrorum. Los resultados indicaron que los aceites esenciales de A. anethoides, A. giraldii, A. roxburghiana y A. rubripes tienen el potencial de ser desarrollados como repelentes para el control de T. castaneum.

Coexistence of resistance to thyroid hormone and ectopic thyroid: ten-year follow-up

SUMMARY Resistance to thyroid hormone (RTH) coexisting with ectopic thyroid is rare. Here we report a case of RTH with ectopic thyroid. A ten-year-old girl had been misdiagnosed as congenital hypothyroidism and treated with levothyroxine since she was born. Ten-year follow-up showed that the elevated thyrotropin was never suppressed by levothyroxine and no signs indicating hyperthyroidism or hypothyroidism despite elevated FT3 and FT4 levels. Therefore the girl developed no defects in physical and cognitive development. Pituitary adenoma was excluded by magnetic resonance imaging. Ultrasonography did not find the thyroid gland in the normal place, while the thyroid scan found a large lingual thyroid gland. The octreotide inhibition test showed a reduction in thyrotropin by 41.98%. No mutation was detected in the thyroid hormone receptor (THR) β, THRα, thyrotropin receptor (TSHR), and GNAS1 genes. To our knowledge, it is an interesting RTH case coexisting with lingual thyroid.

Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil.

Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population-specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (one family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in eight families from the city of Monte Santo in the northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.

Coexistence of resistance to thyroid hormone and ectopic thyroid: ten-year follow-up.

Resistance to thyroid hormone (RTH) coexisting with ectopic thyroid is rare. Here we report a case of RTH with ectopic thyroid. A ten-year-old girl had been misdiagnosed as congenital hypothyroidism and treated with levothyroxine since she was born. Ten-year follow-up showed that the elevated thyrotropin was never suppressed by levothyroxine and no signs indicating hyperthyroidism or hypothyroidism despite elevated FT3 and FT4 levels. Therefore the girl developed no defects in physical and cognitive development. Pituitary adenoma was excluded by magnetic resonance imaging. Ultrasonography did not find the thyroid gland in the normal place, while the thyroid scan found a large lingual thyroid gland. The octreotide inhibition test showed a reduction in thyrotropin by 41.98%. No mutation was detected in the thyroid hormone receptor (THR) ß, THRα, thyrotropin receptor (TSHR), and GNAS1 genes. To our knowledge, it is an interesting RTH case coexisting with lingual thyroid.

Irregularly shaped lacunar infarction: risk factors and clinical significance.

OBJECTIVE: Our study focused on acute lacunar infarct shapes to explore the risk factors and clinical significance of irregularly shaped lacunar infarctions. METHODS: Based on the shape of their acute lacunar infarct, patients (n=204) were classified into the "regular" group or "irregular" group. The characteristics of the lacunar infarction were compared between the regular and irregular groups, between patients with and without neurological deterioration, and between patients with different modified Rankin scale (mRS) scores. The risk factors for irregularly shaped lacunar infarctions, neurological deterioration, and high mRS scores were identified. RESULTS: Blood pressure variability (BPV) was an independent risk factor for irregularly shaped lacunar infarction. Infarction size, prevalence of advanced leukoaraiosis, and irregularly shaped lacunar infarcts were independent risk factors for higher mRS scores. CONCLUSIONS: The irregularly shaped lacunar infarcts were correlated with BPV. Irregularly shaped lacunar infarctions and leukoaraiosis may be associated with unfavorable clinical outcomes.

Irregularly shaped lacunar infarction: risk factors and clinical significance / Infartos lacunares com morfologia irregular: fatores de risco e significado clinico

Objective Our study focused on acute lacunar infarct shapes to explore the risk factors and clinical significance of irregularly shaped lacunar infarctions. Methods Based on the shape of their acute lacunar infarct, patients (n=204) were classified into the “regular” group or “irregular” group. The characteristics of the lacunar infarction were compared between the regular and irregular groups, between patients with and without neurological deterioration, and between patients with different modified Rankin scale (mRS) scores. The risk factors for irregularly shaped lacunar infarctions, neurological deterioration, and high mRS scores were identified. Results Blood pressure variability (BPV) was an independent risk factor for irregularly shaped lacunar infarction. Infarction size, prevalence of advanced leukoaraiosis, and irregularly shaped lacunar infarcts were independent risk factors for higher mRS scores. Conclusions The irregularly shaped lacunar infarcts were correlated with BPV. Irregularly shaped lacunar infarctions and leukoaraiosis may be associated with unfavorable clinical outcomes. .

Objetivo Estudar as diferentes formas dos infartos lacunares agudos, investigando os fatores de risco e o significado clinico daqueles com morfologia irregular. Métodos Os 204 pacientes com infartos lacunares agudos foram classificados em dois grupos: aqueles com morfologia regular e aqueles com morfologia irregular. Foram estudadas as características dos dois grupos e caracterizados os fatores de risco para infartos irregulares, deterioração neurológica e altos escores da escala de Rankin modificada. Resultados Variabilidade da pressão arterial é fator de risco independente para infartos lacunares irregulares. Tamanho do infarto, prevalência de leucoaraiose e formato irregular dos infartos lacunares são fatores de risco independentes para escores mais elevados na escala de Rankin modificada. Conclusões Variabilidade da pressão arterial está relacionada ao formato irregular dos infartos lacunares agudos. Este tipo de infarto e a leucoaraiose podem estar relacionado a desfechos clínicos desfavoráveis. .

Influence of obstructive sleep apnea on serum butyrylcholinesterase activity and ischemia-modified albumin levels.

OBJECTIVE: To investigate the effect of obstructive sleep apnea and continuous positive airway pressure treatment on serum butyrylcholinesterase activity and ischemia-modified albumin levels. METHODS: Thirty-two patients with obstructive sleep apnea and 30 age- and sex-matched controls were enrolled and underwent a diagnostic polysomnogram. The serum butyrylcholinesterase activity, ischemia-modified albumin levels, metabolic parameters, and polysomnography scores were detected and evaluated. Nine patients were studied before and after treatment with continuous positive airway pressure. RESULTS: The serum ischemia-modified albumin levels were significantly higher and the butyrylcholinesterase activity was significantly lower in patients with obstructive sleep apnea than in the controls (p<0.001). The continuous positive airway pressure treatment decreased the modified albumin levels and elevated the buthrylcholinesterase activity (p=0.019 and p=0.023, respectively). The modified albumin levels were positively correlated with the apnea-hypopnea index (r=0.462, p=0.008) at baseline. Elevated ischemia-modified albumin levels can be more accurate than butyrylcholinesterase activity at reflecting the presence of obstructive sleep apnea. Receiver operating characteristic curves revealed a significant difference between the areas under the curve 0.916 for ischemia-modified albumin and 0.777 for butyrylcholinesterase (z=2.154, p=0.031). CONCLUSION: The elevated ischemia-modified albumin level was significantly associated with obstructive sleep apnea and was more sensitive than butyrylcholinesterase activity in reflecting obstructive sleep apnea. The continuous positive airway pressure treatment helped to ameliorate the imbalance.

Influence of obstructive sleep apnea on serum butyrylcholinesterase activity and ischemia-modified albumin levels

OBJECTIVE: To investigate the effect of obstructive sleep apnea and continuous positive airway pressure treatment on serum butyrylcholinesterase activity and ischemia-modified albumin levels. METHODS: Thirty-two patients with obstructive sleep apnea and 30 age- and sex-matched controls were enrolled and underwent a diagnostic polysomnogram. The serum butyrylcholinesterase activity, ischemia-modified albumin levels, metabolic parameters, and polysomnography scores were detected and evaluated. Nine patients were studied before and after treatment with continuous positive airway pressure. RESULTS: The serum ischemia-modified albumin levels were significantly higher and the butyrylcholinesterase activity was significantly lower in patients with obstructive sleep apnea than in the controls (p<0.001). The continuous positive airway pressure treatment decreased the modified albumin levels and elevated the buthrylcholinesterase activity (p = 0.019 and p = 0.023, respectively). The modified albumin levels were positively correlated with the apnea-hypopnea index (r = 0.462, p = 0.008) at baseline. Elevated ischemia-modified albumin levels can be more accurate than butyrylcholinesterase activity at reflecting the presence of obstructive sleep apnea. Receiver operating characteristic curves revealed a significant difference between the areas under the curve 0.916 for ischemia-modified albumin and 0.777 for butyrylcholinesterase (z = 2.154, p = 0.031). CONCLUSION: The elevated ischemia-modified albumin level was significantly associated with obstructive sleep apnea and was more sensitive than butyrylcholinesterase activity in reflecting obstructive sleep apnea. The continuous positive airway pressure treatment helped to ameliorate the imbalance. .

The 'silence' of silent brain infarctions may be related to chronic ischemic preconditioning and nonstrategic locations rather than to a small infarction size.

OBJECTIVE: Silent brain infarctions are the silent cerebrovascular events that are distinguished from symptomatic lacunar infarctions by their 'silence'; the origin of these infarctions is still unclear. This study analyzed the characteristics of silent and symptomatic lacunar infarctions and sought to explore the mechanism of this 'silence'. METHODS: In total, 156 patients with only silent brain infarctions, 90 with only symptomatic lacunar infarctions, 160 with both silent and symptomatic lacunar infarctions, and 115 without any infarctions were recruited. Vascular risk factors, leukoaraiosis, and vascular assessment results were compared. The National Institutes of Health Stroke Scale scores were compared between patients with only symptomatic lacunar infarctions and patients with two types of infarctions. The locations of all of the infarctions were evaluated. The evolution of the two types of infarctions was retrospectively studied by comparing the infarcts on the magnetic resonance images of 63 patients obtained at different times. RESULTS: The main risk factors for silent brain infarctions were hypertension, age, and advanced leukoaraiosis; the main factors for symptomatic lacunar infarctions were hypertension, atrial fibrillation, and atherosclerosis of relevant arteries. The neurological deficits of patients with only symptomatic lacunar infarctions were more severe than those of patients with both types of infarctions. More silent brain infarctions were located in the corona radiata and basal ganglia; these locations were different from those of the symptomatic lacunar infarctions. The initial sizes of the symptomatic lacunar infarctions were larger than the silent brain infarctions, whereas the final sizes were almost equal between the two groups. CONCLUSIONS: Chronic ischemic preconditioning and nonstrategic locations may be the main reasons for the 'silence' of silent brain infarctions.

The 'silence' of silent brain infarctions may be related to chronic ischemic preconditioning and nonstrategic locations rather than to a small infarction size

OBJECTIVE: Silent brain infarctions are the silent cerebrovascular events that are distinguished from symptomatic lacunar infarctions by their 'silence'; the origin of these infarctions is still unclear. This study analyzed the characteristics of silent and symptomatic lacunar infarctions and sought to explore the mechanism of this 'silence'. METHODS: In total, 156 patients with only silent brain infarctions, 90 with only symptomatic lacunar infarctions, 160 with both silent and symptomatic lacunar infarctions, and 115 without any infarctions were recruited. Vascular risk factors, leukoaraiosis, and vascular assessment results were compared. The National Institutes of Health Stroke Scale scores were compared between patients with only symptomatic lacunar infarctions and patients with two types of infarctions. The locations of all of the infarctions were evaluated. The evolution of the two types of infarctions was retrospectively studied by comparing the infarcts on the magnetic resonance images of 63 patients obtained at different times. RESULTS: The main risk factors for silent brain infarctions were hypertension, age, and advanced leukoaraiosis; the main factors for symptomatic lacunar infarctions were hypertension, atrial fibrillation, and atherosclerosis of relevant arteries. The neurological deficits of patients with only symptomatic lacunar infarctions were more severe than those of patients with both types of infarctions. More silent brain infarctions were located in the corona radiata and basal ganglia; these locations were different from those of the symptomatic lacunar infarctions. The initial sizes of the symptomatic lacunar infarctions were larger than the silent brain infarctions, whereas the final sizes were almost equal between the two groups. CONCLUSIONS: Chronic ischemic preconditioning and nonstrategic locations may be the main reasons for the 'silence' of silent brain infarctions.

Characterization of calreticulin expression in mouse endometrium during embryo implantation.

Calreticulin (CRT), a Ca(2+)-binding storage protein and chaperone in the endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca(2+) signaling. However, the role of CRT during implantation remains poorly understood. In the present study, we characterized the expression of CRT mRNA and the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in situ hybridization results showed that the levels of CRT mRNA in the endometria of pregnant mice were significantly higher than those of non-pregnant mice (P<0.05), and increased gradually from pregnancy DI to D4, reaching the máximum level on D4, followed by a plateau from D4 to D7. Using immunofluorescence histochemistry and western blot, changes of CRT expression in the endometria of pregnant mice were consistent with the expression of CRT mRNA. Furthermore, antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant mice (D3) to investígate its effect on embryo implantation. The result showed that the number of implanted embryos markedly decreased in the side of uterine horns receiving antisense CRT oligodeoxynucleotide(í(>)<0.05). These findings suggest that CRT may play an important role in embryo implantation in mice.

Characterization of Calreticulin Expression in Mouse Endometrium during Embryo Implantation

Calreticulin (CRT), a Ca2+-binding storage protein and chaperone in the endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca2+ signaling. However, the role of CRT during implantation remains poorly understood. In the present study, we characterized the expression of CRT mRNA and the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in situ hybridization results showed that the levels of CRT mRNA in the endometria of pregnant mice were significantly higher than those of non-pregnant mice (P<0.05), and increased gradually from pregnancy DI to D4, reaching the máximum level on D4, followed by a plateau from D4 to D7. Using immunofluorescence histochemistry and western blot, changes of CRT expression in the endometria of pregnant mice were consistent with the expression of CRT mRNA. Furthermore, antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant mice (D3) to investígate its effect on embryo implantation. The result showed that the number of implanted embryos markedly decreased in the side of uterine horns receiving antisense CRT oligodeoxynucleotide(í><0.05). These findings suggest that CRT may play an important role in embryo implantation in mice.

Fixed-duration multidrug therapy in multibacillary leprosy

Six-hundred-fifty-seven active multibacillary (MB) leprosy patients were put on fixed-duration multidrug therapy (FD-MDT) between 1985 and 1992 (190 had had no and 235 had had previous treatment with dapsone) and were followed for 5 years after therapy. Two relapses occurred during year 5 of surveillance and both had received dapsone prior to chemotherapy, giving an overall relapse rate of 0.08/100 person-years (py). Excluding the two relapses, 99.4% of the MB patients converted to smear negativity at year 6 after a regular course of FD-MDT. The relapse rate for 35 MB patients with an initial bacterial index (BI) of > 4 with 5 years of surveillance was 0.24/100 py. Reactions occurred more frequently during the first 6 months of MDT, decreasing gradually thereafter, and reaching 0 in year 4 of surveillance. The deformity rate at intake was 22.7% and only 1.8% of MB patients developed new deformities or an increased grade in deformity during therapy.