Heterogeneity in regional changes in body composition induced by androgen deprivation therapy in prostate cancer patients: potential impact on bone health-the BLADE study.

BACKGROUND: It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health. OBJECTIVE: To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers. DESIGN, SETTING, AND PARTICIPANTS: 29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months. INTERVENTION: All patients underwent degarelix administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: T-test or sign test and Pearson or Spearman test for continuous variables were used when indicated. RESULTS AND LIMITATIONS: Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to - 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation. CONCLUSIONS: an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.

Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

Gene count from target sequence capture places three whole genome duplication events in Hibiscus L. (Malvaceae).

BACKGROUND: The great diversity in plant genome size and chromosome number is partly due to polyploidization (i.e. genome doubling events). The differences in genome size and chromosome number among diploid plant species can be a window into the intriguing phenomenon of past genome doubling that may be obscured through time by the process of diploidization. The genus Hibiscus L. (Malvaceae) has a wide diversity of chromosome numbers and a complex genomic history. Hibiscus is ideal for exploring past genomic events because although two ancient genome duplication events have been identified, more are likely to be found due to its diversity of chromosome numbers. To reappraise the history of whole-genome duplication events in Hibiscus, we tested three alternative scenarios describing different polyploidization events. RESULTS: Using target sequence capture, we designed a new probe set for Hibiscus and generated 87 orthologous genes from four diploid species. We detected paralogues in > 54% putative single-copy genes. 34 of these genes were selected for testing three different genome duplication scenarios using gene counting. All species of Hibiscus sampled shared one genome duplication with H. syriacus, and one whole genome duplication occurred along the branch leading to H. syriacus. CONCLUSIONS: Here, we corroborated the independent genome doubling previously found in the lineage leading to H. syriacus and a shared genome doubling of this lineage and the remainder of Hibiscus. Additionally, we found a previously undiscovered genome duplication shared by the /Pavonia and /Malvaviscus clades (both nested within Hibiscus) with the occurrences of two copies in what were otherwise single-copy genes. Our results highlight the complexity of genomic diversity in some plant groups, which makes orthology assessment and accurate phylogenomic inference difficult.

Pathophysiology of Crohn's disease inflammation and recurrence.

Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a TH1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.

Medication-Related Osteonecrosis of the Jaw with Spontaneous Hemimaxilla Exfoliation: Report of a Case in Metastatic Renal Cancer Patient under Multidrug Therapy.

Medication-related osteonecrosis of the jaw (MRONJ) is a well-recognized complication of drug therapies for bone metabolic disorders or cancer related to administration of antiresorptive (bisphosphonates and denosumab) and antiangiogenic drugs. This report describes an advanced and unusual case of stage III peri-implantitis-induced MRONJ involving the right upper jaw which was attempting to self-exfoliate. A 61-year-old male patient, rehabilitated with the placement of two implants when he was still healthy, was suffering from metastatic renal cancer previously treated with bevacizumab, interleukin-2, zoledronic acid, denosumab, cabozantinib and nivolumab. He had been under treatment of nonsurgical therapy over a year, based on antibiotic and antiseptic mouth rinse, without improvement of oral conditions. Surgical treatment consisted of massive sequestrectomy and complete surgical debridement of necrotic bone tissues. The specimen was sent for histopathologic analysis, which confirmed bone tissue necrosis with no evidence of metastatic disease. Two-month follow-up revealed a considerable life quality improvement. Although this complication is well known, the uniqueness of this case is given by its severity, related to the administration of multiple antiresorptive and antiangiogenic drugs, by the natural response of the oral cavity with the almost complete self-exfoliation of the massive necrotic zone. This case is emblematic in highlighting the controversies in the management of MRONJ, which certainly require effective collaboration of the multidisciplinary health care team that could improve patient safety and reduce the risk of developing MRONJ.

Dose-Dependent Effects of Zoledronic Acid on Human Periodontal Ligament Stem Cells: An In Vitro Pilot Study.

Bisphosphonates (BPs) are widely used to treat several metabolic and oncological diseases affecting the skeletal system. Despite BPs' well-known therapeutic potential, they also displayed important side effects, among which is BPs-related osteonecrosis of the jaw, by targeting osteoclast activities, osteoblast, and osteocyte behavior. The aim of this study is to evaluate the biological effects of zoledronic acid (ZOL) in an in vitro model of periodontal ligament stem cells (PDLSCs) by using an experimental setting that resembles the in vivo conditions. PDLSCs were treated with different concentrations of ZOL ranging from 0.1 to 5 µM. The effects of ZOL exposure were evaluated on cell viability via 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazolium bromide (MTT), cell cycle analysis, apoptosis detection, and immunofluorescence. Quantitative real-time polymerase chain reaction (PCR), colorimetric detection of alkaline phosphatase activity, and Alizarin Red S staining were performed to investigate the osteogenic potential of PDLSCs exposed to ZOL. MTT analysis showed that the viability of PDLSCs exposed to ZOL concentration ≥1.5 µM for 3 and 6 days was significantly lower (P < 0.001) than that of untreated cells. The percentage of apoptotic cells was significantly higher in PDLSCs exposed for 4 days to ZOL at 2 µM (P < 0.01) and 5 µM (P < 0.001) when compared to the control. Moreover, ZOL treatment (3 days) accounted for alterations in cell cycle distribution, with an increase in the proportion of cells in G0/G1 phase and a reduction in the proportion of cells in S phase. Chronic exposure (longer than 7 days) of PDLSCs to ZOL accounted for the downregulation of ALP, RUNX2, and COL1 genes at all tested concentrations, which fit well with the reduced alkaline phosphatase activity reported after 7 and 14 days of treatment. Reduced Col1 deposition in the extracellular matrix was reported after 14 days of treatment. Increased calcium deposits were observed in treated cells when compared to the control cultures. In conclusion, chronic exposure to 1 µM ZOL induced significant reduction of osteogenic differentiation, while ZOL concentrations ≥1.5 µM are required to impair PDLSCs viability and induce apoptosis.

The Role of Inflammation in Crohn's Disease Recurrence after Surgical Treatment.

INTRODUCTION: Postoperative recurrence after surgery for Crohn's disease (CD) is virtually inevitable, and its mechanism is poorly known. AIM: To review the numerous factors involved in CD postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives. METHODS: A systematic literature search on CD POR, followed by a review of the main findings. RESULTS: The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation. CONCLUSIONS: POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising.

The Role of Active Inflammation and Surgical Therapy in Crohn's Disease Recurrence.

An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). Several studies demonstrate that severe active inflammation is a strong predictor for surgical complications and recurrence. Indeed, bowel resection in Crohn's disease (CD) patients has a high surgical recurrence rate. In this review, we examined the IBD inflammatory pathways, the current surgical treatments, and the almost inevitable recurrence. The question that might arise is if the cure of intestinal CD is to be found in the surgical approach. A selective search of two databases (PubMed and the Cochrane Library) has been carried out without considering a specific time horizon as inclusion criteria. The scope of this literature review was investigating on the role of inflammation in the management of CD. The following key words have been used to develop the query string: (i) inflammation; (ii) Crohn's disease; (iii) surgery; and (iv) postsurgical recurrence.

Análise da resistência de placas ósseas de acrílico fabricadas a laser quando submetidas a diferentes forças que agem sobre o foco de fratura / Analysis of the resistance of laser-made acrylic bone plates when subjected to different forces acting on the fracture focus

Objetivou-se com este trabalho analisar a resistência de placas ósseas de acrílico, confeccionadas com cortadora a laser CO2, quando submetidas às forças que agem sobre o foco de fratura. Foram utilizados 40 fêmures de ovinos (Ovis aries) e confeccionadas 40 placas de acrílico, os quais foram avaliados em grupos: grupo OP - foram avaliados 20 ossos fraturados reduzidos com 20 placas de acrílico; grupo PS - foram avaliadas 20 placas de acrílico; e grupo OS - foram avaliados 20 ossos íntegros e frescos. Todos foram submetidos a ensaios mecânicos de compressão, flexão, torção e tração, em máquina de ensaios universal EMIC® 10000. Os testes eram interrompidos quando havia fratura do corpo de prova. O grupo PS suportou carga de compressão significativamente superior aos demais grupos OP e OS (13.255±290N, 4.932±827N e 8.681±303N, respectivamente). Já em relação à prova de flexão, o grupo OS foi significativamente mais resistente, com média de 2.698±305N, em relação aos grupos OP e PS, que obtiveram 1.315±92N e 1.537±37N, respectivamente. Conclui-se que as placas de acrílico usinadas a laser apresentam resistência mecânica inferior ao fêmur de ovinos, entretanto, devido à resistência exibida nos testes, demonstraram potencial para serem implantadas em ossos com menor demanda de carga.(AU)

The objective of this work was to analyze the resistance of acrylic bone plates, made with CO 2 laser cutter, when subjected to the forces acting on the fracture focus. Forty ovine femurs (Ovis aries) were used and 40 acrylic plates were prepared and evaluated in groups: In the OP Group, 20 fractured bones reduced with 20 acrylic plates were evaluated; in the PS Group, 20 acrylic plates were evaluated; and in the OS Group 20 intact and fresh bones were evaluated. All were submitted to mechanical tests of compression, bending, twisting and traction in an EMIC® 10000 universal testing machine. The tests were interrupted when the body of proof was fractured. The PS group supported a significantly higher compression load than the other OP and OS groups (13,255±290 N, 4,932±827 N and 8,681±303 N, respectively). Regarding the flexural test, the OS group was significantly more resistant, with a mean of 2,698±305 N, compared to the groups OP and PS that obtained 1,315±92 N and 1,537±37 N respectively. It is concluded that the laser-machined acrylic plates have inferior mechanical resistance to the femur of the ovine, however, due to the presented resistance, it shows potential to be implanted in bones with lower load demand.(AU)

Robot-assisted Partial Nephrectomy and Bilateral Pyelolithotomy in Ectopic Pelvic Kidneys.

OBJECTIVE: To show how to perform a robot-assisted partial nephrectomy and bilateral pyelolithotomy in ectopic pelvic kidneys. This is a congenital abnormality of position and rotation1 frequently associated with urolithiasis.2 Renal cell carcinoma is a very rare event in pelvic kidneys.3,4 These 2 findings in the same patient could be a surgical challenge and whenever possible a "one stage" treatment is preferred. MATERIALS AND METHODS: A 44-year-old male with bilateral pelvic kidneys admitted because of left back pain. Abdominal CT scan showed a 17 mm stone in the left renal pelvis, a 12 mm stones in the right pelvis and a 34 × 27 mm right lower pole renal mass. A robotic surgery was indicated. Patient was placed in Trendelenburg position with ports configuration as for transperitoneal radical prostatectomy. The right kidney was firstly approached: after isolation of the ureter and suspension of the renal artery, a clampless partial nephrectomy was performed; then through a longitudinal pyelotomy the stone was extracted. To minimize the opening of the posterior peritoneum covering the left kidney, the site of the stone was identified by intraoperative ultrasound; then, through a longitudinal pyelotomy the stone was extracted. Given the watertight sutures and the lack of ureteral obstructions no pigtails ureteral catheters were inserted. A Jackson-Pratt drainage was placed through the inferior port. RESULTS: Consolle time was 190 minutes. Estimated Blood Loss (EBL) was 50 ml. No complications were reported. The drain was removed on the second postoperative day, assessed that creatinine dosage was equal to serum. The length of stay was 4 days. Histopathology showed a pT1a G2 clear cell renal cell carcinoma with negative surgical margins, while stones analysis was calcium oxalate. CONCLUSION: With the availability of robotic technology, the indications for minimally invasive surgery may be safely expanded to include concomitant morbidities in uncommon presentations.

Genotoxicity Evaluation of the Soybean Isoflavone Genistein in Human Papillary Thyroid Cancer Cells. Study of Its Potential Use in Thyroid Cancer Therapy.

Genistein is one of the several known isoflavonic phytoestrogens found in a number of plants, with soybeans and soy products being the primary food source. The aim of the study is to evaluate if genistein is able to exert antineoplastic action in primary human papillary thyroid cancer (PTC) cells. Thyroid tissues were treated with genistein (1-10-50-100 µM). Cell viability, proliferation, DNA primary damage and chromosomal damage were evaluated. An antiproliferative effect was induced by the highest doses of genistein, and such an effect was synergistically enhanced by the cotreatment with the antineoplastic drug sorafenib. Comet assay did not show any genotoxic effect in terms of primary DNA damage at all the times (4 and 24 h) and tested doses. A reduction of hydrogen peroxide-induced DNA primary damage in primary thyrocytes from PTC cells pretreated with genistein was observed. Data suggest that genistein exerts antineoplastic action, does not induce genotoxic effects while reduces oxidative-induced DNA damage in primary thyrocytes from PTC cells, supporting its possible use in therapeutic intervention.

CXCL8 and CXCL11 chemokine secretion in dermal fibroblasts is differentially modulated by vanadium pentoxide.

An increase in skin rashes or atopic dermatitis has been observed in individuals working with vanadium. However, to the best of our knowledge no in vivo or in vitro studies have evaluated the effect of exposure to vanadium in dermal fibroblasts. Cells viability and proliferation were assessed by WST­1 assay, cells were treated with increasing concentrations of V2O5 (1, 10 and 100 nM). CXCL8 and CXCL11 concentrations were measured in the supernatants using an ELISA assay. V2O5 was not observed as having a significant effect on dermal fibroblast's viability and proliferation. However, it was revealed that V2O5 was able to induce the secretion of CXCL8 and CXCL11 chemokines into dermal fibroblasts. V2O5 synergistically increased the effect of interferon (IFN)γ on CXCL11 secretion. In addition, V2O5 synergistically increased the effect of the tumor necrosis factor α on CXCL8 secretion and abolished the inhibitory effect of IFNγ. V2O5 induction of CXCL8 and CXCL11 chemokines may lead to the appearance and perpetuation of an inflammatory reaction into the dermal tissue. Further studies are required to evaluate dermal integrity and manifestations in subjects occupationally exposed, or living in polluted areas.

Induction of Th1 chemokine secretion in dermal fibroblasts by vanadium pentoxide.

Vanadium is a soft, silvery­grey metal with a number of different oxidation states. The most common commercial form of vanadium is vanadium pentoxide (V2O5). All vanadium compounds are considered toxic. An increase in skin rashes has been observed in certain vanadium workers, including the development of atopic dermatitis. However, to the best of our knowledge, no prior in vivo or in vitro studies have evaluated the effect of vanadium exposure in human dermal fibroblasts. The present study evaluated the effect of V2O5 on proliferation and chemokine secretion in dermal fibroblasts. The results revealed that V2O5 had no significant effect on the viability or proliferation of fibroblasts, however it was able to induce the secretion of T­helper (Th)1 chemokines from dermal fibroblasts, synergistically increasing the effect of important Th1 cytokines, including interferon­Î³ and tumor necrosis factor­α. Through these processes, V2O5 may lead to the induction and perpetuation of an inflammatory reaction in dermal tissue. The induction and perpetuation of inflammation in the dermis and the variety of involved candidate genes may be at the base of V2O5­induced effects following occupational and environmental exposures. Further studies are necessary to evaluate dermal integrity and manifestations in subjects who are occupationally exposed, or living in polluted areas.

Vanadium pentoxide induces the secretion of CXCL9 and CXCL10 chemokines in thyroid cells.

Vanadium is a grey metal, existing in different states of oxidation, whose most common form in commercial products is vanadium pentoxide (V2O5). All vanadium compounds have been considered toxic. A carcinogenic role of vanadium on the thyroid has recently been proposed. However no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals after exposure to vanadium. In the present study we evaluate the effect of V2O5 on proliferation, and chemokine secretion in normal thyrocytes. Our study demonstrated that V2O5 has no effect on thyroid follicular cell viability or proliferation, but it is able to induce the secretion of T-helper (Th)1 chemokines into the thyroid, synergistically increasing the effect of important Th1 cytokines such as interferon (IFN)γ and tumor necrosis factor (TNF)α. Through this process, V2O5 promotes the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are necessary to evaluate thyroid function, and nodules, in subjects occupationally exposed, or living in polluted areas.

High risk of brain tumors in military personnel: a case control study.

Scientific literature suggests a relationship between military occupation and the development of brain tumors, but no italian study has investigated on the impact of this job on the brain cancer morbidity. In this a study information were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 1999. The study has been conducted as a case-control study. 161, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 483 controls (with other non tumoral neurologic diseases: trauma, hemorrhagic brain disorders, aneurism, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (military vs. non-military occupation). A statistically significant association was seen between brain tumors and military occupation among evaluated patients (p=0.013). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

High risk of brain tumors in farmers: a mini-review of the literature, and report of the results of a case control study.

Even though a relationship between farmer work and the development of brain tumors was suggest by the scientific literature, a small number of italian studies investigate on the impact of this job on the cancer morbidity of farmer population. The informations about this case-control study were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 2000. One hundred and seventy-four, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 522 controls (with other non tumoral neurologic diseases: trauma, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (agricultural vs. non-agricultural). We observed a significant association among brain tumors and rural activity in evaluated patients (P=0.008). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer, particularly in regions where there is an intense agricultural activity and where pesticides are used. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

Avaliação clínica de ovinos após a ingestão de elevada quantidade de manga / Clinical evaluation of sheep after high ingestion of mango fruit

Objetivou-se avaliar clinicamente os efeitos da administração intrarruminal de duas quantidades distintas de manga em ovinos. Foram utilizados sete ovinos machos, hígidos, que não receberam carboidratos não fibrosos por, pelo menos, seis meses previamente ao período experimental, quando se avaliou pH ruminal, total de protozoários no suco de rúmen, pH urinário, pH sanguíneo estimado e parâmetros vitais nos tempos zero, 12, 16, 20 e 24 após a administração da manga. Os sete ovinos foram distribuídos aleatoriamente em dois grupos e receberam 0,625% ou 1,875% da MS de manga/kg/PV (M1 e M2, respectivamente), distribuídos em delineamento cross-over, com uma parcela perdida, e 30 dias de washout. Os ovinos M2 apresentaram valores médios para pH ruminal significativamente inferiores a M1 a partir do tempo T12 (5,1 e 6,9, respectivamente), o que indica ocorrência de acidose ruminal. Os animais tratados com M1 não apresentaram alterações sistêmicas, ao passo que os ovinos tratados com M2 apresentaram acidose metabólica leve, detectada por meio do pH urinário ácido (4,8). A ingestão apenas de manga in natura na quantidade de 1,875% da MS de manga/kg/PV mostrou-se capaz de provocar acidose ruminal em ovinos, levando-os a: ligeira depressão, aumento da frequência cardíaca, diminuição dos movimentos ruminais e diarreia em alguns casos.(AU)

The aim of this study is to clinically evaluate the effects of intra ruminal administration of two different amounts of mango in sheep. The sample was of seven male healthy sheep, which did not receive non-fibrous carbohydrates for at least six months prior to the trial. Rumen fluid pH, total of protozoa in the rumen fluid, urine pH, estimated blood pH, and vital parameters were evaluated at the following times: zero, 12, 16, 20 and 24 hours after administration of the mango. The seven sheep were randomly divided into two groups and received either 0.625% or 1.875% of the dry matter of the pulp and mango peel per kg body weight (M1 and M2, respectively), distributed in cross-over design with a lost portion and 30 days washout. Sheep treated with M2 showed significantly lower average values for ruminal pH than the M1 since T12 (5.1 and 6.9, respectively), indicating the occurrence of ruminal acidosis. The animals treated with M1 showed no systemic changes, while the sheep treated with M2 had mild metabolic acidosis, detected through the lower urinary pH (4.8). The in natura mango ingestion in the amount of 1.875% of the dry matter of mango per kg of body weight proved to provoke rumen acidosis in sheep, leading these animals to: slight depression, rise in heart rate, diminished rumen movement, and diarrhea in some cases.(AU)

Both 3,5-diiodo-L-thyronine (T2) and T3 modulate glucose-induced insulin secretion.

3,5-diiodo-L-thyronine (T2), a naturally existing iodothyronine, has biological effects on humans, but no information is available on its action on pancreatic b-cells. We evaluated its effect vs triiodothyronine (T3), on glucose-induced insulin secretion in INS-1e cells, a rat insulinoma line, and on human islets. INS-1e were incubated in the presence/absence of T2 or T3 (0.1 nmol/L-10 µmol/L), and glucose (3.3, 7.5, 11.0, and 20 mmol/L). Insulin release and content (at 11.0 and 20 mmol/L glucose) were significantly (p less than 0.01) stimulated by 1-100 nmol/L T2 and 0.1 nmol/L-1.0 µmol/L T3, and inhibited with higher concentrations of both (1–10 µmol/L T2 and 10 µmol/L T3). Human islets were incubated with 3.3 mmol/L glucose in presence/absence of T3 or T2 (0.1 nmol/L, 0.1 µmol/L, and 1 µmol/L). T2 (0.1 nmol/L-0.1 µmol/L) significantly (p less than0.01) stimulated insulin secretion, while higher concentrations (1 µmol/L) inhibited it. A modest increase in insulin secretion was evidenced with 1 µmol/L T3. In conclusion, T2 and T3 have a direct regulatory role in insulin secretion, depending on their concentrations and the glucose level itself. At concentrations near the physiological range, T2 enhances glucose-induced insulin secretion in both rat b-cells and human islets.