Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine. RESULTS: We found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years. CONCLUSIONS: Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD.

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

OBJECTIVE: To standardize a technique for ventilating rat fetuses with Congenital Diaphragmatic Hernia (CDH) using a volume-controlled ventilator.METHODS: Pregnant rats were divided into the following groups: a) control (C); b) exposed to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses of the three groups were randomly divided into the subgroups ventilated (V) and non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed and ventilated for 30 minutes using a volume-controlled ventilator. Then the lungs were collected for histological study. We evaluated: body weight (BW), total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW, morphological histology of the airways and causes of failures of ventilation.RESULTS: BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N- (p <0.05) and CDH (p <0.05), but no differences were found between the subgroups V and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in groups N- and CDH, with no difference between V and N-V (p <0.05). The C and N- groups could be successfully ventilated using a tidal volume of 75 ìl, but the failure of ventilation in the CDH group decreased only when ventilated with 50 ìl.CONCLUSION: Volume ventilation is possible in rats with CDH for a short period and does not alter fetal or lung morphology.

Teaching project: a low-cost swine model for chest tube insertion training

Objective: to describe and evaluate the acceptance of a low-cost chest tube insertion porcine model in a medical education project in the southwest of Paraná, Brazil. Methods: we developed a low-cost and low technology porcine model for teaching chest tube insertion and used it in a teaching project. Medical trainees - students and residents - received theoretical instructions about the procedure and performed thoracic drainage in this porcine model. After performing the procedure, the participants filled a feedback questionnaire about the proposed experimental model. This study presents the model and analyzes the questionnaire responses. Results: seventy-nine medical trainees used and evaluated the model. The anatomical correlation between the porcine model and human anatomy was considered high and averaged 8.1±1.0 among trainees. All study participants approved the low-cost porcine model for chest tube insertion. Conclusion: the presented low-cost porcine model for chest tube insertion training was feasible and had good acceptability among trainees. This model has potential use as a teaching tool in medical education.

Stretch Injuries of Skeletal Muscles: Experimental Study in Rats' Soleus Muscle

The study aimed to verify the physiological injury behavior by stretching the soleus muscle of rats, using a noninvasive experimental model. Twenty-four rats were used and divided into three groups of eight animals: control group (A), group that performed tetanus followed by electrical stimulation and a sudden dorsiflexion of the left paw performed by a device equipped with a mechanism of muscle soleus rapid stretching (B); and a group that only received the tetanus (C). Three days later, the animals were killed, and the soleus muscle was resected and divided into three segments. Morphological changes indicative of muscle damage appeared in all three segments of group B. In a lesser degree, similar changes were also detected in muscles subjected to only tetanus. This model was effective; reproducing an injury similar to what occurs in human sports injuries.

Uso precoce e tardio de dopamina após isquemia miocárdica

OBJETIVO: Avaliar os efeitos na função ventricular esquerda do uso precoce e tardio de dopamina, em modelo experimental de coração isolado. MÉTODO: Foram utilizados 60 coelhos em modelo de coração isolado mantido por animal suporte. Um balão intraventricular foi locado no ventrículo esquerdo. Três grupos foram constituídos: grupo controle (GC); grupo que recebeu dopamina precoce (Dopa P) e grupo que recebeu dopamina tardia (após 20 minutos) (Dopa T). Foram realizadas leituras hemodinâmicas diretas e indiretas. RESULTADOS: Fluxo sangüíneo coronariano: GC(7,196 ± 1,275ml/min); Dopa P (9,477 ± 1,160ml/min); Dopa T (14,316 ± 2,308ml/min), com GC=Dopa P, GC ¹Dopa T e Dopa P¹Dopa T. Primeira derivada temporal da pressão intraventricular (dp/dt+): GC (719,61 ± 127,53ml/min); Dopa P (719,61 ± 127,53ml/min); Dopa T (1431,60 ± 230,87ml/min), p<0,05, Dopa P¹Dopa T, GC=Dopa P e GC ¹ Dopa T. Primeira derivada temporal da pressão intraventricular negativa (dp/dt-): GC (469,85 ± 107,16mmHg/s); Dopa P (716,07 ± 215,66mmHg/s); Dopa T (931,24 ± 181,46mmHg/s), p<0,05, Dopa P¹Dopa T¹GC. Delta V: GC (1,355 ± 0,2432ml); Dopa P (0,97 ± 0,3199ml); Dopa T (1,27 ± 0,2983ml), p>0,05, Dopa P=Dopa T=GC. Estresse sistólico desenvolvido: GC (27,273 ± 10,276g/cm²); Dopa P (55,219 ± 24,625g/cm²); Dopa T (79,152 ± 12,166g/cm²), Dopa P=Dopa T, Dopa P=GC e GC ¹ Dopa T.Dialdeído Malônico (MDA): GC (4,5 ± 0,527mmol/L); Dopa P (4,7 ± 1,16mmol/L); Dopa T (4,1 ± 0,7379mmol/L), p>0,05, Dopa P=Dopa T=GC. CONCLUSÕES: Concluiu-se que, no modelo experimental delineado, o uso precoce da dopamina foi deletério, segundo algumas variáveis hemodinâmicas.

Modelos experimentais de deficiência limbar em coelhos: análise clínica

Objetivo: Comparar em coelhos três modelos experimentais de destruição das células germinativas (CG) do limbo corneano quanto a aspectos clínicos. Métodos: Foram utilizados 54 coelhos, 108 olhos, subdivididos em 3 grupos experimentais: (G1), (G2) e (G3), cada um formado pelos OE de 18 coelhos, submetidos às técnicas experimentais (T1), (T2) e (T3), respectivamente, e um grupo controle, formado pelos 54 olhos contralaterais (OD). Nas três técnicas foi utilizado o n-heptanol. Na T1, o n-heptanol foi aplicado por 5 minutos, para remoção do epitélio límbico. Na T2, além da aplicação do n-heptanol, realizou-se peritomia e remoção da conjuntiva perilímbica até 4 mm do limbo, juntamente com a escarificação do tecido episcleral. Na T3, além dos procedimentos da T2, foi realizada dissecção lamelar do limbo abrangendo aproximadamente 1,5 mm na periferia da córnea e 2 mm na superfície escleral. em todas as córneas dos animais foram estudados seis parâmetros clínicos: neovascularização, perda da transparência, irregularidade da superfície, reparação epitelial, erosão ou defeito epitelial, granuloma e outras lesões corneanas. Resultados: A neovascularização corneana iniciou-se mais precocemente com a T1 e T2; ocorreu em 100% dos casos com as três técnicas, de forma não homogênea, variando de leve a intensa; permaneceu estável a partir do 28º dia até o final do experimento (56º dia), foi maior nos quadrantes superior e inferior e menor nos quadrantes nasal e temporal. A perda da transparência e a irregularidade da superfície corneana foram menores com a T1 que com a T2 e T3, que foram similares entre si. Houve, nas três técnicas experimentais, latência de três dias para o início da reepitelização, que se completou com a T1 no 7º dia e com a T2 e T3 no 14º dia. Erosão epitelial corneana e granuloma corneano foram encontradas de forma similar nas três técnicas experimentais. Conclusões: A T2 e T3 mostraram-se adequadas como possíveis modelos de ampla remoção das CG límbicas, levando a resultados similares nos diversos parâmetros estudados. A T1 se mostrou adequada como modelo de remoção parcial do epitélio límbico. Ocorreu conjuntivalização e neovascularização nas três técnicas experimentais.

Clinical evaluation and induced corneal vascularization study by native and anionic collagen membranes in rabbits corneas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Clinical and radiographic changes around dental implants inserted in different levels in relation to the crestal bone, under different restoration protocols, in the dog model

Background: The aim of the present study was to evaluate clinical and radiographic changes that occur around dental implants inserted in different levels in relation to crestal bone under different restoration protocols.Methods: Thirty-six implants were inserted in the edentulous mandible of six mongrel dogs. Each implant was assigned to an experimental group according to the distance from the top of the implant to the crestal bone: Bone Level (at crestal bone level), Minus 1 (1 mm below crestal bone), or Minus 2 (2 mm below crestal bone). Each hemimandible was submitted to a restoration protocol: conventional (prosthesis was installed 120 days after implant placement, including 30 days with healing cap) or immediate (prosthesis was installed 24 hours after implant placement). Fixed partial prostheses were installed bilaterally in the same day. After 90 days, clinical and radiographic parameters were evaluated.Results: As long as the implants were inserted in more apical positions, the first bone-to-implant contact (fBIC) was positioned more apically (P<0.05). However, the apical positioning of the implants did not influence the ridge loss or the position of the soft tissue margin (PSTM) (P>0.05). In addition, in immediately restored sites, the PSTM was located significantly more coronally than that in conventionally restored sites (P=0.02).Conclusions: Despite the more apical positioning of the fBIC, the height of the peri-implant soft tissues and ridge was not jeopardized. Moreover, the immediate restoration protocol was beneficial to the maintenance of the PSTM. Further studies are suggested to evaluate the significance of these results in longer healing periods.

Experimental pulmonary paracoccidioidomycosis in the Syrian hamster: morphology and correlation of lesions with the immune response.

A model for pulmonary paracoccidioidomycosis in the hamster is described. The disease was induced by intratracheal inoculation of 1.7 x 10(5) viable yeast forms of P. brasiliensis. Lung histopathology, dissemination lesions and humoral and cellular immune responses were investigated at intervals up to 24 weeks after infection. Humoral immunity was studied by immunodiffusion and complement fixation tests. Cell-mediated immunity was evaluated in vitro by the macrophage migration inhibition test in the presence of phytohaemagglutinin and P. brasiliensis soluble antigen, and in vivo by the paracoccidioidin test. Thirty out of 35 infected animals (85.7%) developed pulmonary paracoccidioidomycosis. Dissemination lesions were observed in regional lymph nodes (82.8%), liver (8.5%) and spleen (5.7%). Lung involvement was mainly around bronchi and vessels. Regional lymph nodes were severely involved from the fourth week on, acquiring a pseudotumoral aspect at later stages. Specific antibodies were detected from the fourth week on, with titres increasing progressively. The cellular immune response to phytohaemagglutinin was intact throughout the experiment and the response to P. brasiliensis antigen was already detectable by the second week and remained positive to the end of the experiment. The skin test became positive from the fourth week on. Inoculation by the intratracheal route represents a highly effective way of infecting hamsters with P. brasiliensis, with the induction of localized disease, good antibody production and intact cell immunity.

Alterações histológicas de glândulas submandibulares e testículos induzidas por dietas à base de soja e dieta zinco deficiente em ratos.

The purpose of this study was to examine in rats the histologic alterations of the submandibular glands and testicles induced by soy diets and zinc deficient diet. The zinc deficiency produced testicles alterations including seminiferous tubulus atrophy, germinative epithelium degeneration, spermatogenesis alterations and a significant atrophy of the submandibular glands which presented no much delimitated acines. The soy diet without complementations also compromised the spermatogenesis by showing seminiferous tubulus atrophied and a reduction of the germinative epithelium. The soy diet complemented by saline and vitaminic mixtures didn't produced testicles alterations but its induced in the submandibular glands a hypertrophy of the ductal component mainly in relation to the granular component.