Angiotensin II increases parathyroid hormone-related protein (PTHrP) and the type 1 PTH/PTHrP receptor in the kidney

Angiotensin II (AngII) participates in the pathogenesis of kidney damage. Parathyroid hormone (PTH)-related protein (PTHrP), a vasodilator and mitogenic agent, is upregulated during renal injury. The aim of this study was to investigate the potential relation between AngII and PTHrP system in the kidney. Different methods were used to find that both rat mesangial and mouse tubuloepithelial cells express PTHrP and the type 1 PTH/PTHrP receptor (PTH1R). In these cells, AngII increased PTHrP mRNA and protein production. In contrast, PTH1R mRNA was increased in mesangial cells and downregulated in tubular cells, but its protein levels were unmodified in both cells. AT(1) antagonist, but not AT(2), abolished AngII effects on PTHrP/PTH1R. The in vivo effect of AngII was further investigated by systemic infusion (a low dose of 50 ng/kg per min) into normal rats. In controls, PTHrP immunostaining was mainly detected in renal tubules. In AngII-infused rats, PTHrP staining increased in renal tubules and appeared in the glomerulus and the renal vessels. After AngII infusion, PTHR1 staining was markedly increased in all these renal structures at day 3 but remained elevated only in tubules at day 7. The AT(1) antagonist, but not the AT(2), significantly diminished AngII-induced PTHrP and PTHR1 overexpression in the renal tissue, associated with a decrease in tubular damage and fibrosis. The results indicate that AngII regulates renal PTHrP/PTH1R system via AT(1) receptors. These findings demonstrate that PTHrP upregulation occurs in association with the mechanisms of AngII-induced kidney injury.     

Nicotinic modulation in an animal model of a form of associative learning impaired in Alzheimer's disease

Eyeblink classical conditioning is a widely used associative learning paradigm that has striking behavioral and neurobiological parallels between humans and other mammals. Eyeblink conditioning is impaired in older organisms, and patients with Alzheimer's disease (AD) are impaired beyond the normal aging deficit. The cholinergic system is of demonstrated involvement in eyeblink conditioning. Blockade of nicotinic cholinergic receptors with mecamylamine prolonged acquisition of conditioned responses (CRs) in young adult rabbits, and the nicotinic agonist, GTS-21 ameliorated conditioning deficits in older rabbits. Galantamine induces allosteric modulation of nicotinic cholinergic receptors to increase acetylcholine release as well as acting as an acetylcholinesterase inhibitor. Galantamine doses of 0.0, 1.0, 2.0, 3.0, and 4.0 mg/kg were tested in ten daily sessions in 40 retired breeder rabbits (mean age = 29 months) in the 750 ms delay conditioning paradigm. A dose of 3 mg/kg galantamine was effective in improving conditioning in older rabbits, enabling them to achieve learning criterion rapidly and to produce a very high percentage of CRs. Control tests of rabbits in explicitly unpaired conditions demonstrated that non-associative factors could not account for the results. The efficacy of galantamine in a learning paradigm that shows severe impairment in AD indicates that the drug may be effective as a cognition-enhancer in AD.     

The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women.

High levels of circulating insulin-like growth factor-I (IGF-I) and its major binding protein (IGFBP-3) at premenopausal ages have been associated with an increased breast cancer risk. We conducted a cross-sectional study (215 premenopausal women and 241 after natural menopause) nested within the Guernsey prospective studies to examine the relationship between the IGF system and mammographic features of the breast. The mammographically dense area in the breast increased with increasing serum levels of IGF-I (P for linear trend, P(t) = 0.05), IGF-II (P(t) = 0.08), and IGFBP-3 (P(t) = 0.01) only in premenopausal women. IGF-II and IGFBP-3 serum levels were associated with increases in the mammographically lucent area in both premenopausal (P(t) = 0.01 and 0.04, respectively) and postmenopausal women (P(t) < 0.001 for both), but these associations were no longer statistically significant after adjustment for body mass index and waist circumference. Neither the IGF-I/IGFBP-3 nor the IGF-II/IGFBP-3 molar ratio was associated with any of these mammographic features. The number of A alleles at a polymorphic locus in the promoter region of the IGFBP-3 gene was associated with increasing mean IGFBP-3 levels in both premenopausal (P(t) = 0.01) and postmenopausal (P(t) <0.001) women but not with mammographically dense area. These results support the hypothesis that the IGF system may affect the amount of mammographically dense tissue in premenopausal women, possibly by promoting cell proliferation and inhibiting apoptosis in the fibroglandular tissue. The findings also show strong relations between IGF-II and IGFBP-3 levels and the amount of mammographically lucent tissue, reflecting the associations between body adiposity and amount of fat tissue in the breast and between body adiposity and circulating levels of these growth factors.     

Characterization of familial Waldenstrom's macroglobulinemia.

BackgroundFamilial clustering of B-cell disorders among Waldenström's macroglobulinemia (WM) patients has been reported, though the frequency and any differences in disease manifestation for familial patients remain to be defined.Patients and methodsWe therefore analyzed clinicopathological data from 257 consecutive and unrelated WM patients. Forty-eight (18.7%) patients had at least one first-degree relative with either WM (n = 13, 5.1%), or another B-cell disorder including non-Hodgkin's lymphoma (n = 9, 3.5%), myeloma (n = 8, 3.1%), chronic lymphocytic leukemia (n = 7, 2.7%), monoclonal gammopathy of unknown significance (n = 5, 1.9%), acute lymphocytic leukemia (n = 3, 1.2%) and Hodgkin's disease (n = 3, 1.2%). Patients with a familial history of WM or a plasma cell disorder (PCD) were diagnosed at a younger age and with greater bone marrow involvement.ResultsDeletions in 6q represented the only recurrent structural chromosomal abnormality and were found in 13% of patients, all non-familial cases. Interphase FISH analysis demonstrated deletions in 6q21-22.1 in nearly half of patients, irrespective of familial background.ConclusionsThe above results suggest a high degree of clustering for B-cell disorders among first-degree relatives of patients with WM, along with distinct clinical features at presentation based on familial disease cluster patterns. Genomic studies to delineate genetic predisposition to WM are underway.     

Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development.

Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.     

体重指数、代谢综合征和白细胞计数间的关系

肥胖和代谢综合征(M S)常常并存,两者都与心血管风险的增加有关。白细胞计数的增加也与心血管风险的增加有关。然而,人们对肥胖独立于M S之外的作用尚有争议。本研究拟评估M S对无症状患者肥胖与白细胞计数之间关系的影响。研究数据来自431例拟行心血管风险评估的无症状巴西男性(平均年龄46±7岁)。M S被定义为至少存在下列危险因素中的3项:高血压(≥130/85m m H g)、躯体肥胖(≥102cm)、高甘油三酯血症(≥1500m g/L)、高密度脂蛋白胆固醇水平低(≤400m g/L)以及高血糖(血糖≥1100m g/L)。肥胖的定义是体重指数≥30kg/m2。记录混杂变量…     

Cesarean section as a cause of chronic pelvic pain.

OBJECTIVE: To determine if the history of cesarean section was associated with chronic pelvic pain, independent of the presence of other conditions such as pelvic adhesions, endometriosis, sequelae of pelvic inflammatory disease, leiomyoma and pelvic varices. METHODS: Retrospective case-control study conducted on 199 patients consecutively admitted from January 1998 to January 2000, 116 of them submitted to laparoscopy for the diagnosis of chronic pelvic pain and 83 asymptomatic patients submitted to tubal ligation by laparoscopy. A logistic regression analysis was used to verify the association between chronic pelvic pain and the history of previous cesarean section. RESULTS: In women with chronic pelvic pain, a history of cesarean section was observed in 67.2% of cases, adhesions in 51.7%, endometriosis in 33.6%, sequelae of pelvic inflammatory disease in 31.9%, leiomyoma in 6.9% and pelvic varices in 11.2%. In asymptomatic women, a history of cesarean section was observed in 38.5%, adhesions in 24.1%, endometriosis in 9.6%, sequelae of pelvic inflammatory disease in 4.8%, leiomyoma in 7.2% and pelvic varices in 3.6%. In a logistic model, chronic pelvic pain was associated with a history of cesarean section (O.R.=3.7), as well as with endometriosis (O.R.=8.5), sequelae of pelvic inflammatory disease (O.R.=10.5). CONCLUSIONS: In the present study cesarean section was associated with chronic pelvic pain. This fact may be the cause of a public health problem in the coming years, due to the raised rates of cesarean section in Brazilian women.     

Hashimoto's thyroiditis and Sjögren syndrome. Association or autoimmune multiple syndrome?

A case of Hashimoto's thyroiditis associated with incomplete Sj?gren's syndrome is revised. Both immune disorders are together not just as a casual event, but literature says that common mechanisms could have something to be. Previous publications express that autoimmune thyroid dysfunction is frequently associated with primary Sj?gren's syndrome and should be sought clinically and by laboratory test in all these patients.     

Transverse myelopathy in an adult with acute lymphoblastic leukemia: case report

We report a case of transverse myelopathy in a 31 year old white man with acute lymphoblastic leukemia, subtype L3 (ALL-L3). This is a severe form of leukemia that affects children more often than adults. Less than 1% of leukemic patients develop neurologic complication in the spinal cord. The symptomatology in the present case started with back pain, flaccid paraplegia, and loss of sensibility and vegetative functions below the lesion. The etiologic diagnostic was obtained through peripheral blood study, bone marrow cytology, cerebrospinal fluid analysis and magnetic resonance image of the dorsal cord. The antileukemic treatment with specific drugs had no influence on the fatal outcome of the disease.