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1.
BMC Geriatr ; 23(1): 722, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940840

RESUMO

BACKGROUND: To study the effect of hip fracture type on physical performance, functional ability and change in mobility four to six months after the injury. METHODS: A total of 1331 patients out of consecutive 2052 patients aged ≥ 65 years who underwent hip fracture surgery were included in the study. Patient information was collected on admission, during hospitalization, by phone interview and at the geriatric outpatient clinic 4 to 6 months after the fracture. Of the 1331 eligible patients, Grip strength, Timed Up and Go -test (TUG), Elderly Mobility Scale (EMS), mobility change compared to pre-fracture mobility level, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) were used to determine physical performance and functional ability. Logistic regression was used for the analyses which was adjusted for gender, age, American Society of Anesthesiologists score, diagnosis of cognitive disorder, pre-fracture living arrangements, mobility and need of mobility aid. RESULTS: Patients with pertrochanteric hip fracture had an EMS lower than 14 (Odds Ratio (OR) 1.38, 95% confidence intervals (CI) 1.00-1.90), TUG time ≥ 20 s (OR 1.69, 95% CI 1.22-2.33) and they had declined in mobility (OR 1.58, 95% CI 1.20-2.09) compared to femoral neck fracture patients 4 to 6 months post-hip fracture in multivariable-adjusted logistic regression analyses. Grip strength and functional ability (IADL, BADL) 4 to 6 months after hip fracture did not differ between fracture types. There were no statistically significant differences in physical performance in patients with a subtrochanteric fracture compared to patients with a femoral neck fracture. CONCLUSIONS: Pertrochanteric hip fracture independently associated with poorer physical performance 4 to 6 months post hip fracture compared to other hip fracture types. Pertrochanteric hip fracture patients should be given special attention in terms of regaining their previous level of mobility.


Assuntos
Fraturas do Colo Femoral , Fraturas do Quadril , Idoso , Humanos , Atividades Cotidianas , Estudos Prospectivos , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Hospitalização
2.
Aging Clin Exp Res ; 34(9): 2107-2116, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35727456

RESUMO

BACKGROUND: Hip fracture causes not only physical injury but also psychological trauma. Fear of falling (FoF) is related to poor recovery, loss of mobility and mortality. There is limited data on the clinical factors affecting post-hip fracture FoF and its consequences. OBJECTIVE: To investigate the factors associated with and 1-year outcomes of post-hip fracture FoF. METHODS: An observational prospective cohort study. Data were collected on hospital admission, at a geriatric outpatient assessment 4-6 months post-hip fracture and by telephone interviews 1 year after the index fracture. FoF was assessed with a dichotomous single-item question. Logistic regression analyses were conducted to examine the age, gender and multivariable-adjusted association between baseline and the geriatric assessment domains with FoF. Follow-up outcomes included changes in mobility, living arrangements and mortality. RESULTS: Of the 916 patients included, 425 (49%) had FoF at the time of their geriatric assessment. These patients were predominantly female and were living alone in their own homes with supportive home care. They scored lower on tests of physical performance. Less FoF was documented in patients with diagnosed cognitive disorders before the index fracture and in those with Clinical Dementia Rating ≥ 1. After adjusting for age and gender, no association was observed between FoF and any of the 1-year follow-up outcomes. CONCLUSION: Post-hip fracture FoF is common and associated with female gender, polypharmacy, poor daily functioning, poor physical performance and depressive mood. Patients with cognitive disorders have less FoF than those without. FoF appears to have no impact on the follow-up outcomes.


Assuntos
Avaliação Geriátrica , Fraturas do Quadril , Idoso , Medo/psicologia , Feminino , Fraturas do Quadril/complicações , Humanos , Masculino , Estudos Prospectivos
3.
Aging Clin Exp Res ; 34(6): 1407-1418, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34984652

RESUMO

BACKGROUND: Incontinence and hip fractures are common in older people, especially women, and associated with multiple adverse effects. Incontinence is a risk factor for falls. AIMS: We aimed to investigate the prevalence of urinary (UI) and double incontinence (DI, concurrent UI and faecal incontinence), and to identify factors associated with UI and DI 6 months post-fracture. METHODS: A prospective real-life cohort study was conducted consisting of 910 women aged ≥ 65 who were treated for their first hip fracture in Seinäjoki Central Hospital, Finland, between May 2008 and April 2018. Continence status was elicited at baseline and 6 months postoperatively at our geriatric outpatient clinic where all participants underwent a multidisciplinary comprehensive geriatric assessment (CGA) consisting of an evaluation of cognition, nutrition, mood, mobility, and functional ability. RESULTS: At baseline, 47% of the patients were continent, 45% had UI and 8% had DI, and at follow up, 38%, 52%, and 11%, respectively. The mean age of the patients was 82.7 ± 6.8. Both UI and DI were associated with functional disability and other factors related to frailty. The associations were particularly prominent for patients with DI who also had the worst performance in the domains of CGA. We identified several modifiable risk factors: depressive mood (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.16-2.84) and constipation (OR 1.48, 95% CI 1.02-2.13) associated with UI and, late removal of urinary catheter (OR 2.33, 95% CI 1.31-4.14), impaired mobility (OR 2.08, 95% CI 1.05-4.15), and poor nutrition (OR 2.31, 95% CI 1.11-4.79) associated with DI. CONCLUSIONS: This study demonstrates a high prevalence of UI and DI in older women with hip fracture and modifiable risk factors, which should be targeted in orthogeriatric management and secondary falls prevention. Patients with DI were found to be an especially vulnerable group.


Assuntos
Incontinência Fecal , Fraturas do Quadril , Incontinência Urinária , Idoso , Estudos de Coortes , Incontinência Fecal/epidemiologia , Feminino , Avaliação Geriátrica , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Estudos Prospectivos , Fatores de Risco , Incontinência Urinária/epidemiologia
4.
Arch Gerontol Geriatr ; 107: 104901, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36521394

RESUMO

OBJECTIVES: To investigate the association of urinary incontinence (UI) and double incontinence (DI, concurrent UI and fecal incontinence) with one-year mortality among older female hip fracture patients and to identify predictors of incident UI and DI. DESIGN: A prospective cohort study SETTING AND SUBJECTS: 1,468 female patients aged ≥ 65 treated for their first hip fracture during the period 2007-2019 METHODS: Continence status was elicited at baseline and one-year post-fracture. Age- and multivariable-adjusted Cox proportional hazards and multinomial logistic regression models were used to determine the associations of incontinence with one-year mortality and to examine the associations of baseline predictors with incident UI and DI respectively. RESULTS: Of the women with no incontinence, UI and DI, 78 (13%), 159 (23%) and 60 (34%), died during follow-up. UI (HR 1.72, 95% CI 1.31-2.26) and DI (HR 2.61, 95% CI 1.86-3.66) were associated with mortality after adjusting for age. These associations lost their predictive power in multivariable analysis while age over 90, living in an institution, impaired mobility, poor nutrition, polypharmacy, and late removal of urinary catheter remained associated with mortality. Of continent women, 128 (21%) developed UI and 23 (4%) DI during follow-up. In multivariable analysis, impaired mobility was associated with incident UI (OR 2.56, 95% CI 1.48-4.44) and DI (OR 4.82, 95% CI 1.70-13.7), as well as living in an institution (OR 3.44, 95% CI 1.56-7.61 and OR 3.90, 95% CI 1.17-13.0). CONCLUSIONS AND IMPLICATIONS: Underlying vulnerability likely explains differences in mortality between continence groups and development of incident UI and DI.


Assuntos
Incontinência Fecal , Fraturas do Quadril , Incontinência Urinária , Humanos , Feminino , Idoso , Estudos Prospectivos , Incontinência Urinária/complicações , Fraturas do Quadril/complicações , Sobreviventes , Fatores de Risco
5.
Scand J Urol ; 55(1): 72-77, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32964777

RESUMO

PURPOSE: Possible genetic background and autoimmune etiology of Bladder Pain Syndrome (BPS, formerly Interstitial Cystitis, IC) has been suggested. We studied whether familial clustering of BPS, other autoimmune diseases or fibromyalgia exist among BPS patients' genetically close relatives; possibly reflecting some common predisposing genetic background of these diseases. MATERIALS AND METHODS: Altogether 420 first- or second-degree relatives of 94 BPS patients fulfilling the NIDDK criteria were asked to fill in a survey on the self-reported diagnosis of urinary tract diseases, fibromyalgia and 23 autoimmune diseases, together with filling the O'Leary-Sant symptom score. The ones with high symptom scores were interviewed and, if necessary, referred to a further clinical consultation. The prevalence of other diseases was compared to previously published prevalence percentages. RESULTS: 334 (80%) of 420 family members returned the questionnaire. Only one of the relatives fulfilled the NIDDK criteria, and one sibling pair among the original BPS patients was found. Asthma, ulcerative colitis, fibromyalgia, iritis and rheumatoid arthritis were more common in the study population than in the reference populations. The reported prevalence of atopic dermatitis and rhinoconjunctivitis causing allergies were lower. In addition, the results show that the O'Leary-Sant symptom score is not reliable in screening for new BPS cases. CONCLUSIONS: Our study suggests that in BPS patients' families, fibromyalgia and autoimmune diseases including asthma, and especially the non-allergic form of asthma, may be over-represented.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Cistite Intersticial/genética , Adulto , Doenças Autoimunes/complicações , Estudos de Coortes , Estudos Transversais , Cistite Intersticial/complicações , Feminino , Fibromialgia/complicações , Fibromialgia/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
6.
Acta Vet Scand ; 59(1): 46, 2017 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-28701213

RESUMO

BACKGROUND: Severe outbreaks of interdigital phlegmon (IP) associated with a high morbidity and major economic losses have occurred in Finland in the past decade. A survey was performed to indicate the current occurrence of infectious hoof diseases and to identify herd level risk factors predisposing to an outbreak of IP. RESULTS: Responses to a questionnaire revealed that an outbreak of IP defined as morbidity ≥5% within the 1st month of the outbreak, had occurred in 18.0% of the respondent study farms. Risk factors for an outbreak included animal transport between herds, i.e. either animal purchase or contract heifer rearing, enlargement or renovation of the barn, and if the fields of the farm had been organically cultivated. Having any kind of mechanical ventilation in comparison to natural ventilation seemed to lower the risk of IP. Additionally, the farms that had experienced an outbreak of IP often had other infectious hoof diseases. However, it was unclear which disease appeared first. CONCLUSIONS: More attention is needed before and during enlargement or renovation of the barn and substantial planning is crucial for every part of the enlargement process in dairy farms.


Assuntos
Criação de Animais Domésticos , Doenças dos Bovinos/epidemiologia , Celulite (Flegmão)/veterinária , Surtos de Doenças/veterinária , Doenças do Pé/veterinária , Casco e Garras , Animais , Bovinos , Doenças dos Bovinos/etiologia , Doenças dos Bovinos/prevenção & controle , Celulite (Flegmão)/epidemiologia , Celulite (Flegmão)/prevenção & controle , Indústria de Laticínios , Feminino , Finlândia/epidemiologia , Doenças do Pé/epidemiologia , Doenças do Pé/prevenção & controle , Fatores de Risco , Inquéritos e Questionários
7.
Nephron Exp Nephrol ; 101(2): e50-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15956810

RESUMO

BACKGROUND: The anion transporters SLC26A6 (PAT1) and SLC26A7, transporting at least chloride, oxalate, sulfate and bicarbonate, show a distinct expression and function in different mammalian species. They are expressed in kidney, but their exact localization in human kidney has not been studied. We therefore examined SLC26A6 and A7 expression in human kidneys. METHODS: The localization of SLC26A6 and A7 in different segments of human nephrons was studied by RT-PCR and immunohistochemistry by comparing to the tubular markers PNRA, CD10, Tamm-Horsfall antigen, high molecular weight cytokeratin, CK7, AQP2 and H(+)V-ATPase. RESULTS: In human kidney, SLC26A6 is expressed in distal segments of proximal tubules, parts of the thin and thick ascending limbs of Henle's loops, macula densa, distal convoluted tubules and a subpopulation of intercalated cells of collecting ducts. SLC26A7 is expressed in extraglomerular mesangial cells and a subpopulation of intercalated cells of collecting ducts. CONCLUSION: Our results show that in human kidney SLC26A6 and A7 have a distinct, partially overlapping expression in distal segments of nephrons. The distribution partly differs from that found previously in rodent kidneys.


Assuntos
Antiporters/metabolismo , Rim/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Adulto , Animais , Antiporters/genética , Células COS , Criança , Pré-Escolar , Chlorocebus aethiops , Embrião de Mamíferos/metabolismo , Imunofluorescência , Humanos , Lactente , Recém-Nascido , Rim/embriologia , Proteínas de Membrana Transportadoras/genética , Rim Displásico Multicístico/metabolismo , Néfrons/metabolismo , Rim Policístico Autossômico Dominante/metabolismo , RNA Mensageiro/metabolismo , Transportadores de Sulfato , Distribuição Tecidual
8.
Prev Vet Med ; 94(1-2): 18-27, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20116112

RESUMO

The Finnish Healthy Hooves Project was set up to determine the frequency of, and risk factors for, various hoof lesions in Finnish dairy herds. Data were collected in 2003 and 2004. A large data set of >74,000 cow-level observations recorded by hoof-trimmers were merged with production data from the Finnish Agricultural Data Processing Centre Ltd. Ultimately, data from a single lactation from each of 16,727 cows in 703 herds were used for analyses of white-line disease (WLD) and haemorrhages-lesions. Three-level hierarchical logistic models with hoof-trimmer and farms (within hoof-trimmer) as random-effects were fit to datasets of tie-stall (TS) and loose-housing (LH) herds separately. Cows examined once had a WLD risk of 4.8% in TS herds and 17% in LH herds. As the number of examinations increased, the odds of a WLD diagnosis increased substantially; (2 and 3+ examinations had odds ratios (ORs) of 2.57 and 3.40 in TS herds and 2.32 and 4.67 in LH herds, respectively, compared to 1 examination). Parity had an interaction with breed in all models in TS and in the LH haemorrhages model, but not in WLD LH models. In TS herds, older Holstein cows had a very high risk of WLD compared to young Ayrshire cows (OR=7.92). Also in LH herds both breed and parity had association with WLD (Holstein cows were 1.57 times more likely than Ayrshire cows and cows in parity >or=4 were more likely (OR=2.89) than parity 1 to get WLD). In TS herds, other hoof lesions - such as haemorrhages (OR=1.65), heel-horn erosions (OR=1.77), and corkscrew claw (OR=1.82) - increased the risk of WLD. In LH herds, corkscrew claw (OR=1.59) and heel-horn erosion (OR=0.72) had a significant association with WLD. In TS herds, use of mats (compared to hard flooring) significantly reduced the risk of WLD and haemorrhages (OR=0.57 and OR=0.80, respectively). No significant associations of the 305-day milk production on the risk of either disease were observed in either TS or LH herds (305-day milk yield from each cows' previous lactation were used for calculations, with herd average yield and the individual cow's deviation from the herd average being used as predictors).


Assuntos
Doenças dos Bovinos/epidemiologia , Indústria de Laticínios/métodos , Doenças do Pé/veterinária , Casco e Garras/patologia , Abrigo para Animais , Bem-Estar do Animal , Animais , Cruzamento , Bovinos , Doenças dos Bovinos/etiologia , Doenças dos Bovinos/patologia , Feminino , Finlândia/epidemiologia , Doenças do Pé/epidemiologia , Doenças do Pé/patologia , Úlcera do Pé/epidemiologia , Úlcera do Pé/patologia , Úlcera do Pé/veterinária , Lactação/fisiologia , Coxeadura Animal , Modelos Logísticos , Razão de Chances , Paridade , Gravidez , Fatores de Risco , Índice de Gravidade de Doença
9.
Prev Vet Med ; 89(3-4): 227-36, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19297047

RESUMO

The Finnish Healthy Hooves project was set up to determine the frequency of, and risk factors for various hoof lesions in Finnish dairy herds. Data were collected in the years 2003 and 2004. A large dataset of over 74,000 cow-level observations recorded by hoof trimmers was merged with production data from the Finnish Agricultural Data Processing Centre Ltd. Ultimately, data from a single lactation from each of 16,792 cows in 703 herds were used for the analyses in this paper. Three-level hierarchical logistic models with hoof trimmer and farms (within hoof trimmer) as random effects were fit to data sets of tie stall (TS) and loose housing (LH) herds separately. The outcome of interest was the presence or absence of a sole ulcer in one or more legs of a cow during the lactation of interest. Cows examined once had a risk of sole ulcer 5.23% in tie stall herds and 7.58% in LH herds. As the number of examinations increased the odds of a diagnosis of sole ulcer increased substantially (2 and 3+ examinations had odds ratios (ORs) of 1.42 and 3.42 in TS herds and 2.77 and 6.89 in LH herds). Breed had a large effect on the risk of sole ulcer with Holsteins 2.89 times more likely to be affected than Ayrshires in TS herds and 2.94 times in LH herds. In TS herds, the presence of other hoof lesions such as haemorrhages (OR = 2.97), heel-horn erosions (OR = 2.10) and corkscrew claw (OR = 2.83) increased the risk of a sole ulcer developing. In LH herds, only haemorrhages (OR = 1.80) were a significant risk factor when parity was > or = 2. In TS herds, use of mats (compared to hard flooring) significantly reduced the risk of sole ulcers (OR = 0.49). The effect of parity on the risk of sole ulcer was greatest when parity > or = 4 but this effect was only significant in tie stalls (OR = 1.86). When analyses were restricted to cows with parity > or = 2, similar results were obtained for the risk factors identified above. In addition, parity became highly significant in TS and LH (OR 2.31 and 2.23, respectively when parity was 4+). In TS herds, herd average milk production was significantly associated with a decrease risk of sole ulcer (OR = 1.28 per 1000 kg decrease) but there was no effect of production at the cow level (measured as deviation from the herd mean). No significant effects of production were observed in LH herds.


Assuntos
Doenças dos Bovinos/epidemiologia , Úlcera do Pé/veterinária , Casco e Garras/patologia , Abrigo para Animais , Paridade , Criação de Animais Domésticos/métodos , Animais , Cruzamento , Bovinos , Doenças dos Bovinos/etiologia , Doenças dos Bovinos/patologia , Indústria de Laticínios , Feminino , Finlândia/epidemiologia , Úlcera do Pé/epidemiologia , Úlcera do Pé/etiologia , Úlcera do Pé/patologia , Modelos Logísticos , Razão de Chances , Gravidez , Fatores de Risco
10.
Cancer Genet Cytogenet ; 183(2): 83-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18503824

RESUMO

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome predisposing to cutaneous and uterine leiomyomatosis as well as renal cell cancer and uterine leiomyosarcoma. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC. On occasion, no FH mutation is detected by direct sequencing, despite the evident HLRCC phenotype in a family. In the present study, to investigate whole gene or exonic deletions and amplifications in FH mutation-negative patients, we used multiplex ligation-dependent probe amplification technology. The study material comprised 7 FH mutation-negative HLRCC patients and 12 patients affected with HLRCC-associated phenotypes, including papillary RCC, early-onset RCC, uterine leiomyomas, or uterine leiomyosarcoma. A novel FH mutation, a deletion of FH exon 1 that encodes the mitochondrial signal peptide, was detected in one of the HLRCC patients (1/7). The patient with the FH mutation displayed numerous painful cutaneous leiomyomas and papillary type renal cell cancer. Our finding, together with the two patients with whole FH gene deletion who had been detected previously, suggests that exonic or whole-gene FH deletions are not a frequent cause of HLRCC syndrome.


Assuntos
Carcinoma de Células Renais/genética , Éxons , Fumarato Hidratase/genética , Leiomiomatose/genética , Mutação , Deleção de Sequência , Sequência de Bases , Primers do DNA , Humanos , Reação em Cadeia da Ligase
11.
Nephrol Dial Transplant ; 22(12): 3462-70, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17804457

RESUMO

In the present study, the effect of potassium depletion on the expression of acid-base transporters in the collecting duct was examined. Toward this end rats were fed a potassium-free diet for 3 weeks. Thereafter, the expression of the basolateral chloride/bicarbonate exchangers AE1 and SLC26A7 and the apical H(+)-ATPase was examined by northern hybridization, immunoblot analysis and immunofluorescence labelling. The mRNA expression of AE1 increased by a robust approximately 500% in the cortex and approximately 70% in the outer medulla, which translated into a huge increase in AE1 protein abundance in the cortex and a moderate increase in the outer medulla in K-depletion. The mRNA expression of SLC26A7 did not change significantly but its protein abundance showed a robust increase in the outer medulla. The expression of SLC26A7 remained undetected in the cortex in K-depleted rats. The post translational increase in SLC26A7 membrane abundance in potassium depletion was recapitulated in vitro using epitope-tagged SLC26A7. H(+)-ATPase displayed enhanced apical plasma membrane immunoreactivity in the OMCD in K-depletion. We suggest that the up-regulation of SLC26A7 and AE1 on the basolateral membrane of A-intercalated cells in the OMCD and CCD, respectively, along with H(+)-ATPase on the apical membrane, contributes to enhanced bicarbonate absorption in the collecting duct in K-depletion.


Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/fisiologia , Antiporters/fisiologia , Túbulos Renais Coletores/fisiologia , Potássio/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Transportadores de Sulfato
12.
Reproduction ; 133(4): 775-84, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17504921

RESUMO

Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na(+)/H(+) exchanger 3 (NHE3), the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na(+)/H(+) exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted.


Assuntos
Epididimo/química , Transporte de Íons/fisiologia , Proteínas de Membrana Transportadoras/análise , Ducto Deferente/química , Adulto , Idoso , Proteínas de Transporte de Ânions/análise , Antiporters/análise , Anidrase Carbônica II/análise , Regulador de Condutância Transmembrana em Fibrose Cística/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/análise , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/análise , Transportadores de Sulfato , Fixação de Tecidos , ATPases Vacuolares Próton-Translocadoras/análise
13.
Fertil Steril ; 85(1): 232-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16412765

RESUMO

Male subfertility in congenital chloride diarrhea (CLD) was possible after identification of expression of an epithelial Cl-/HCO3- exchanger SLC26A3 in the male reproductive tract and by the observation that adult men with CLD had very few children. A prospective clinical and laboratory study among eight adult Finnish men with CLD revealed constant oligoasthenoteratozoospermia but normal spermatogenesis, high chloride and low pH in seminal plasma, and three spermatoceles, suggesting that male subfertility is a clinical manifestation of CLD and could be caused by an analogous defect in the epithelial Cl-/HCO3- and water transport, as described for the CLD intestine.


Assuntos
Antiporters/genética , Antiporters/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Adolescente , Adulto , Bicarbonatos/metabolismo , Antiportadores de Cloreto-Bicarbonato , Cloretos/metabolismo , Diarreia/genética , Diarreia/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Sêmen/metabolismo , Transportadores de Sulfato , Desequilíbrio Hidroeletrolítico/genética , Desequilíbrio Hidroeletrolítico/metabolismo
14.
Am J Physiol Cell Physiol ; 284(3): C769-79, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12444019

RESUMO

The solute carrier gene family SLC26 consists of tissue-specific anion exchanger genes, three of them associated with distinct human recessive disorders. By a genome-driven approach, several new SLC26 family members have been identified, including a kidney- and pancreas-specific gene, SLC26A6. We report the functional characterization of SLC26A6 and two new alternatively spliced variants, named SLC26A6c and SLC26A6d. Immunofluorescence studies on transiently transfected cells indicated membrane localization and indicated that both NH(2)- and COOH-terminal tails of the SLC26A6 variants are located intracellularly, suggesting a topology with an even number of transmembrane domains. Functional expression of the three proteins in Xenopus oocytes demonstrated Cl(-) and SO(4)(2-) transport activity. In addition, the transport of SO(4)(2-) and Cl(-) was inhibited by DIDS and HCO(3)(-). We demonstrated also that the COOH terminus of SLC26A6 binds to the first and second PDZ domains of the Na(+)/H(+) exchanger (NHE)3 kinase A regulatory protein (E3KARP) and NHE3 regulatory factor (NHERF) proteins in vitro. Truncation of the last three amino acids (TRL) of SLC26A6 abrogated the interaction but did not affect transport function. These results demonstrate that SLC26A6 and its two splice variants can function as anion transporters linked to PDZ-interaction pathways. Our results support the general concept of microdomain organization for ion transport and suggest a mechanism for cystic fibrosis transmembrane regulator (CFTR)-mediated SLC26A6 upregulation in pancreatic duct cells.


Assuntos
Antiporters/metabolismo , Membrana Celular/metabolismo , Células Eucarióticas/metabolismo , Transporte de Íons/genética , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Processamento Alternativo/genética , Animais , Antiporters/genética , Células COS , Membrana Celular/genética , Antiportadores de Cloreto-Bicarbonato/genética , Antiportadores de Cloreto-Bicarbonato/metabolismo , Cloretos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Proteínas do Citoesqueleto/metabolismo , Feminino , Humanos , Oócitos , Fosfoproteínas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína/genética , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Trocadores de Sódio-Hidrogênio , Transportadores de Sulfato , Sulfatos/metabolismo , Xenopus laevis
15.
J Am Soc Nephrol ; 15(8): 2002-11, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15284286

RESUMO

SLC26A7 is a recently identified Cl(-)/HCO(3)(-) exchanger that co-localizes with AE1 on the basolateral membrane of Alpha intercalated cells (A-IC) in outer medullary collecting duct (OMCD). The purpose of these studies was to determine whether AE1 and SLC26A7 are differentially regulated in OMCD in pathophysiologic states. Toward this end, the expression and regulation of AE1 and SLC26A7 was examined in water deprivation, a condition known to increase the osmolality of the medulla. Rats were subjected to 3 d of water deprivation while having free access to food. Northern hybridizations demonstrated that in the outer medulla, the mRNA expression of SLC26A7 increased by approximately 300% (P < 0.01 versus control; n = 3), whereas the expression of AE1 decreased by approximately 50% (P < 0.05 versus control, n = 3) in water-deprived rats. Immunoblot analysis studies demonstrated that in the outer medulla, SLC26A7 abundance increased by approximately 3.5-fold (P < 0.02 versus control; n = 3), whereas the AE1 abundance decreased by approximately 55% (P < 0.05 versus control) in water deprivation. The expression of SLC26A7 remained unchanged in the kidney cortex and stomach in water deprivation, indicating the specificity of SLC26A7 upregulation in outer medulla. In situ hybridization indicated the exclusive expression of SLC26A7 in the outer medulla and double immunofluorescence labeling confirmed the co-localization of AE1 and SLC26A7 on the basolateral membrane of A-IC cells in OMCD. It is concluded that AE1 and SLC26A7 are differentially regulated in OMCD in water deprivation. On the basis of these results and previous functional studies indicating the activation of SLC26A7 activity by high osmolality, it is proposed that SLC26A7 may play an important role in bicarbonate reabsorption and or cell volume regulation in OMCD (specifically under hypertonic conditions).


Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Antiporters/metabolismo , Bicarbonatos/metabolismo , Cloretos/metabolismo , Túbulos Renais Coletores/metabolismo , Animais , Proteína 1 de Troca de Ânion do Eritrócito/genética , Antiporters/genética , Feminino , Imunofluorescência , Expressão Gênica , Medula Renal/metabolismo , Ratos , Ratos Sprague-Dawley , Transportadores de Sulfato , Privação de Água/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia
16.
J Biol Chem ; 277(16): 14246-54, 2002 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-11834742

RESUMO

A second distinct family of anion exchangers, SLC26, in addition to the classical SLC4 (or anion exchanger) family, has recently been delineated. Particular interest in this gene family is stimulated by the fact that the SLC26A2, SLC26A3, and SLC26A4 genes have been recognized as the disease genes mutated in diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome, respectively. We report the expansion of the SLC26 gene family by characterizing three novel tissue-specific members, named SLC26A7, SLC26A8, and SLC26A9, on chromosomes 8, 6, and 1, respectively. The SLC26A7-A9 proteins are structurally very similar at the amino acid level to the previous family members and show tissue-specific expression in kidney, testis, and lung, respectively. More detailed characterization by immunohistochemistry and/or in situ hybridization localized SLC26A7 to distal segments of nephrons, SLC26A8 to developing spermatocytes, and SLC26A9 to the lumenal side of the bronchiolar and alveolar epithelium of lung. Expression of SLC26A7-A9 proteins in Xenopus oocytes demonstrated chloride, sulfate, and oxalate transport activity, suggesting that they encode functional anion exchangers. The functional characterization of the novel tissue-specific members may provide new insights to anion transport physiology in different parts of body.


Assuntos
Ânions , Antiporters/química , Proteínas de Transporte/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Transporte de Ânions , Antiporters/genética , Northern Blotting , Clonagem Molecular , DNA Complementar/genética , Éxons , Humanos , Imuno-Histoquímica , Hibridização In Situ , Íntrons , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Transportadores de Sulfato , Distribuição Tecidual , Xenopus
17.
Am J Physiol Renal Physiol ; 286(1): F161-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12965893

RESUMO

The outer medullary collecting duct (OMCD) plays an important role in bicarbonate reabsorption and acid-base regulation. An apical V-type H+-ATPase and a basolateral Cl-/HCO3- exchanger, located in intercalated cells of OMCD, mediate the bicarbonate reabsorption. Here we report the identification of a new basolateral Cl-/HCO3- exchanger in OMCD intercalated cells in rat kidney. Northern hybridizations demonstrated the predominant expression of this transporter, also known as SLC26A7, in the outer medulla, with lower expression levels in the inner medulla. SLC26A7 was recognized as a approximately 90-kDa band in the outer medulla by immunoblot analysis and was localized on the basolateral membrane of a subset of OMCD cells by immunocytochemical staining. No labeling was detected in the cortex. Double-immunofluorescence labeling with the aquaporin-2 and SLC26A7 antibodies or anion exchanger-1 and SLC26A7 antibodies identified the SLC26A7-expressing cells as alpha-intercalated cells. Functional studies in oocytes demonstrated that increasing the osmolality of the media (to simulate the physiological milieu in the medulla) increased the Cl-/HCO3- exchanger activity mediated via SLC26A7 by about threefold (P < 0.02 vs. normal condition). We propose that SLC26A7 is a basolateral Cl-/HCO3- exchanger in intercalated cells of the OMCD and may play an important role in bicarbonate reabsorption in medullary collecting duct.


Assuntos
Antiporters/genética , Antiporters/metabolismo , Antiportadores de Cloreto-Bicarbonato/genética , Antiportadores de Cloreto-Bicarbonato/metabolismo , Túbulos Renais Coletores/fisiologia , Animais , Proteína 1 de Troca de Ânion do Eritrócito/genética , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Bicarbonatos/metabolismo , Cloretos/metabolismo , Feminino , Imunofluorescência , Soluções Hipertônicas , Immunoblotting , Medula Renal/fisiologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Transportadores de Sulfato
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