The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures. MAIN BODY: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals. CONCLUSION: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.

Diagnostic, treatment, and follow-up of osteoporosis-position statement of the Latin American Federation of Endocrinology.

The Latin American Federation of Endocrinology position statement on osteoporosis was developed by endocrinologists from 9 countries. It encompasses the definition, diagnosis, treatment, and follow-up of the disease, the identification of barriers to healthcare, and proposals to improve the disease care in the region. INTRODUCTION: There is a gap in the understanding of osteoporosis in Latin America. The objective of this work is to state the position of the Latin American Federation of Endocrinology on osteoporosis care in postmenopausal women to better bridge this gap. METHODS: An experts' panel was formed comprising of 11 endocrinologists from 9 countries. A data search was conducted with a conceptual approach and data selection was based on the hierarchy of the EBHC pyramid. Unpublished data was considered for local epidemiological data and expert opinion for the identification of barriers to healthcare. An expert consensus based on the Delphi methodology was carried out. Experts were asked to respond on a 5-point Likert Scale to two provided answers to guiding questions. RESULTS: Consensus was agreed on the answer for the questions with the higher median on the Likert scale and synthetized on 16 statements covering the definition of osteoporosis, diagnostic approach, treatment options, and follow-up. Besides clinical topics, unmet needs in osteoporosis were identified in relation to local epidemiological data, barriers to treatment, and misclassification of programs within health systems. CONCLUSIONS: Through a process based on recognized methodological tools, FELAEN's position on osteoporosis was developed. This made it possible to state an optimum scenario for the care of the disease and helped to identify knowledge gaps. There is great variability in the approach to osteoporosis in Latin America and barriers in all the stages of healthcare persist.

Sarcopenia in Type 2 Diabetes Mellitus: A Cross-Sectional Observational Study.

BACKGROUND: The aim of this study was to compare the prevalence of low muscle mass and sarcopenia in patients with type 2 diabetes mellitus (T2DM) versus paired controls (control group, CG) and the association between sarcopenia and chronic diabetes complications. METHODS: Men and women ≥50 years with T2DM (T2DM group, T2DMG) were recruited during routine outpatient visits. Total body densitometry and handgrip strength (HGS) were evaluated in the T2DMG and CG, while the T2DMG was also evaluated for the physical performance using the gait speed (GS) test. Sarcopenia was diagnosed according to the criteria of the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). RESULTS: The study included 177 individuals in the T2DMG and 146 in the CG. The mean HGS value was lower in the T2DMG (24.4 ± 10.3 kg) compared with the CG (30.9 ± 9.15 kg), p < 0.001, with low HGS in 46 (25.9%) and 10 (9%) in the T2DMG and CG, respectively (p < 0.001). The prevalence of sarcopenia defined according to the FNIH criteria was higher in the T2DMG 23 (12.9%) compared with the CG 8 (5.4%), p < 0.03. The presence of albuminuria increased the odds of sarcopenia (odds ratio (OR) 2.84, 95% confidence interval (CI) 1.07-7.68, p=0.04) and osteoporosis (OR 3.38, 95% CI 1.12-9.89, p=0.03), even in patients with mild to moderate nephropathy. The body composition analysis showed increased odds of sarcopenia with increased percentage of total fat (%TF) in women (OR 1.18, 95% CI, 1.03-1.43, p=0.03) and men (OR 1.31, 95% CI, 1.10-1.75, p=0.01). CONCLUSION: Patients with T2DM presenting with albuminuria, osteoporosis, and increased %TF were more likely to have sarcopenia. This finding emphasizes the need for patients with T2DM to be evaluated for sarcopenia to allow for early implementation of measures to prevent or treat this disorder.

A comprehensive study on crystal structure of a novel sulfonamide-dihydroquinolinone through experimental and theoretical approaches.

Quinolinones and sulfonamides are moieties with biological potential that can be linked to form new hybrid compounds with improved potential. However, there are few hybrids of these molecules reported. In this sense, this work presents a structural description of a new sulfonamide-dihydroquinolinone (E)-2-(2-methoxyphenyl)-3-(3-nitrobenzylidene)-1-(phenylsulfonyl)-2,3 dihydroquinolin-4(1H)-one (DHQ). The molecular structure of DHQ was elucidated by X-ray diffraction, nuclear magnetic resonance and infrared spectroscopy, and both molecular packing and intermolecular interactions were analyzed by Hirshfeld surfaces and fingerprint maps. In addition, theoretical calculations on frontier orbitals, molecular electrostatic potential maps, and assignments were performed. The crystal packing of DHQ was found to be stabilized by a dimer through a weak C-H⋯O interaction along the c axis. Moreover, the structure is stabilized mainly by C-H⋯O and C-H⋯π interactions, since the interaction C25-H25⋯π contributes to a chain formation. The Hirshfeld normalized surface shows that the closest interactions are around the atoms linked to the dimer formation. The calculations indicate that DHQ possesses electrophilic sites near O atoms and depleted electrons around the H atoms. There is a band GAP of 3.29 eV between its frontier orbitals, which indicates that DHQ is more reactive than other analogues published.

Comparison of sweat rate during graded exercise and the local rate induced by pilocarpine.

Centrally stimulated sweat rate produced by graded exercise until exhaustion was compared to the local sweat rate induced by pilocarpine, often used as a sweating index for healthy individuals. Nine young male volunteers (22 +/- 4 years) were studied in temperate environment in two situations: at rest and during progressive exercise with 25 W increases every 2 min until exhaustion, on a cycle ergometer. In both situations, sweating was induced on the right forearm with 5 ml 0.5% pilocarpine hydrochloride applied by iontophoresis (1.5 mA, 5 min), with left forearm used as control. Local sweat rate was measured for 15 min at rest. During exercise, whole-body sweat rate was calculated from the body weight variation. Local sweat rate was measured from the time when heart rate reached 150 bpm until exhaustion and was collected using absorbent filter paper. Pharmacologically induced local sweat rate at rest (0.4 +/- 0.2 mg cm-2 min-1) and mean exercise-induced whole-body sweat rate (0.4 +/- 0.1 mg cm-2 min-1) were the same (P > 0.05) but were about five times smaller than local exercise-induced sweat rate (control = 2.1 +/- 1.4; pilocarpine = 2.7 +/- 1.2 mg cm-2 min-1), indicating different sudorific mechanisms. Both exercise-induced whole-body sweat rate (P < 0.05) and local sweat rate (P < 0.05) on control forearm correlated positively with pilocarpine-induced local sweat rate at rest. Assuming that exercise-induced sweating was a result of integrated physiological mechanisms, we suggest that local and whole-body sweat rate measured during graded exercise could be a better sweating index than pilocarpine.

Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p<0.001). In particular, those with lower BV/TV (<50th percentile) had significantly lower Cn.CaMean (p=0.037) and higher Cn.CaLow (p=0.020) compared with those with higher (>50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone mineralization pattern. However, the observed concomitant occurrence of relatively lower bone volumes with lower bone matrix mineralization will both contribute to the reduced aBMD in some patients with COPD.

Partial aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome) in two brothers.

We report on two brothers (in a sibship of three) with partial aniridia, cerebellar ataxia, and moderate mental retardation, with normal G-banded chromosomes. Both present cerebellum hypoplasia; the younger also has congenital pulmonic stenosis. A review of the literature is presented. Cause is unknown, although the possibility of an autosomal recessive gene cannot be ruled out.

Epidemiological study of eye injuries in Brazilian children.

A year-long follow-up study of 146 eye injuries in children up to 15 years of age was carried out in two emergency hospitals of a southern Brazilian city. These injuries represent approximately 65% of the total number of patients seeking ophthalmic care at emergency hospitals within this city. Patients were followed up for at least four months after injury; visual results as well as epidemiological factors were analyzed. Based on these findings, children in the 0- to 5-year-old group were at greatest risk, regardless of sex; among children older than 5 years, eye injuries were more frequent in boys. Generally, the child takes part in the accident as an active participant, and adequate adult supervision decreases the number of these accidents. Analysis of the relationship between socioeconomic levels of the parents and severity of eye injuries revealed that severe eye injuries were more frequent in lower socioeconomic strata. In severe eye injuries 35.1% of the children ended with visual acuity under 20/200 in the affected eye, which corresponds to 9% of all studied eye injuries.

Effects of aluminum on the mechanical and electrical activity of the Langendorff-perfused rat heart.

The effect of aluminum (Al3+) chloride (1, 5, 10, 50 and 100 microM) on myocardial electromechanical activity was studied in 10 Langendorff-perfused hearts from adult female Wistar rats. Al3+ decreased the development of isovolumic systolic pressure from 34.3 +/- 2.95 mmHg under control conditions to 11.8 +/- 1.53 mmHg at 100 microM AlCl3 (P < 0.01) (diastolic pressure = 0 mmHg). The atrial and ventricular rates also decreased, but only with AlCl3 concentrations greater than 1 microM (from 180 +/- 5 to 94 +/- 11 bpm for atrial rate and from 180 +/- 5 to 78 +/- 7 bpm for ventricular rate). Reduction of coronary flow was also observed, reaching 60% at 100 microM Al3+. A delay in atrioventricular conduction occurred at 10 microM Al3+, increasing progressively up to 100 microM (62.3 +/- 4 ms in the Al(3+)-free solution to 143 +/- 34 ms in the presence of 100 microM Al3+, P < 0.01, ANOVA). QRS duration did not change as a function of increasing Al3+ concentrations (37.1 +/- 1.7 ms in the Al(3+)-free solution vs 32.1 +/- 1.6 ms in the presence of 100 microM Al3+). No qualitative changes in ECG were observed. These data show that the toxic effects of Al3+ on the myocardium are reflected in reduced systolic pressure development and coronary flow and increased PR interval. These effects are discussed in terms of the inhibition of nucleotide hydrolysis by Al3+.

Heat storage rate and acute fatigue in rats.

Thermal environmental stress can anticipate acute fatigue during exercise at a fixed intensity (%VO2max). Controversy exists about whether this anticipation is caused by the absolute internal temperature (Tint, degrees C), by the heat storage rate (HSR, cal/min) or by both mechanisms. The aim of the present study was to study acute fatigue (total exercise time, TET) during thermal stress by determining Tint and HSR from abdominal temperature. Thermal environmental stress was controlled in an environmental chamber and determined as wet bulb globe temperature ( degrees C), with three environmental temperatures being studied: cold (18 degrees C), thermoneutral (23.1 degrees C) or hot (29.4 degrees C). Six untrained male Wistar rats weighing 260-360 g were used. The animals were submitted to exercise at the same time of day in the three environments and at two treadmill velocities (21 and 24 m/min) until exhaustion. After implantation of a temperature sensor and treadmill adaptation, the animals were submitted to a Latin square experimental design using a 2 x 3 factorial scheme (velocity and environment), with the level of significance set at P<0.05. The results showed that the higher the velocity and the ambient temperature, the lower was the TET, with these two factors being independent. This result indicated that fatigue was independently affected by both the increase in exercise intensity and the thermal environmental stress. Fatigue developed at different Tint and HSR showed the best inverse relationship with TET. We conclude that HSR was the main anticipating factor of fatigue.

[Virus search in cerebrospinal fluid in Vogt-Koyanagi syndrome: report of a case]. / Pesquisa de vírus no líquido cefalorraqueano na síndrome de Vogt-Koyanagi: registro de um caso.

Research was carried out on isolating and identification of a virus in the cerebrospinal fluid of a patient with the Vogt-Koyanagi syndrome (uveomeningeal encephalitis). Results were negative. It was not possible to detect any virus causing the disease in this case. This research was the first such study carried out in Brazil.

[Vogt-Koyanagi syndrome. Report of a case in a pregnant woman]. / Síndrome de Vogt-Koyanagi. Relato de um caso em gestante.

A 28 year old pregnant woman with Vogt-Koyanagi syndrome is reported. Despite the use of steroid therapy, she became blind. She delivered a boy Apgar 8. The newborn developed a meningoencephalitis in the nursery and died two years later with evidence of cerebral palsy. Correlation between both mother and son disease has not been found.

Sudomotor responses from glabrous and non-glabrous skin during cognitive and painful stimulations following passive heating.

AIM: It is widely accepted that thermal and psychological sweating are independently controlled and respectively restricted to non-glabrous (hairy) and glabrous skin. These assumptions were evaluated in six experiments conducted across eight body segments, in which 38 glabrous and non-glabrous skin surfaces were investigated. METHODS: Sweating was measured in 30 passively heated individuals using ventilated sweat capsules, with passive heating used to first establish steady-state sweating, averaging 0.30 mg cm(-2) min(-1) (±0.03) across all sites, prior to the application of cognitive and painful stimuli. RESULTS: These non-thermal (psychological) stimulations significantly increased sweat secretion at more than 70% of the sites investigated [cognitive: 28 of 38 sites (P < 0.05); pain: 23 of 32 sites (P < 0.05)], eliciting peak sweat rates averaging 0.51 mg cm(-2) min(-1) (±0.05) and 0.47 mg cm(-2) min(-1) (±0.4 respectively) across all sites. Furthermore, non-thermal sweating was evident from both the glabrous and non-glabrous surfaces and occurred without mean body or local skin temperatures changes (P > 0.05). Indeed, neither thermal nor psychological sweating was restricted to discrete skin surfaces, and there were no consistent sudomotor differences between these two skin classifications. Finally, at no site was thermal sweating inhibited during a non-thermal stimulation. CONCLUSION: These generalized sudomotor responses challenge the hypotheses that glabrous skin sweating is driven by psychological stimuli, and that thermal sweating is a phenomenon restricted to the non-glabrous skin surfaces.

Changes in eccrine sweating on the glabrous skin of the palm and finger during isometric exercise.

AIM: The goals of this study were to investigate changes in the sweating and cutaneous vascular responses on the palm and the volar aspect of the index finger during sustained static exercise of increasing intensity and to determine whether the former can be attributed to altered sweat gland activity. METHODS: Five male and five female subjects performed maximal voluntary handgrip contractions (MVC: right hand) for 60 s at 20, 35 and 50% MVC (ambient temperature 25 °C, relative humidity 50%). RESULTS: The sweat rate and the number of activated sweat glands on the non-exercised hand showed intensity-dependent increases (P < 0.05). At 35 and 50% MVC, finger sweat secretion was significantly higher than on the palm, which was primarily associated with the number of activated sweat glands (P < 0.05). In addition, there was a marked simultaneous decrease in the cutaneous vascular conductance for the finger at 35 and 50% MVC (P < 0.05), but not for the palm. CONCLUSION: Our results suggest that a difference exists between intensity-dependent increases of sudomotor responses within more than one glabrous skin site. Specifically, markedly greater sweating occurs on the volar finger than on the palmar surface during sustained static exercise. These differences in sweat rate mainly resulted from changes in the number of activated sweat glands. In addition, intra-segment variations in cutaneous blood flow on the glabrous hand are shown.

Nonsuture colonic anastomosis.

Methyl-2-cyanoacrylate was used for nonsuture end-to-end anastomosis of the ascending colon in 35 male Sprague-Dawley rats. The results were studied in seven sacrificed rats and eight rats that died after the procedure. The mortality rate was 22 per cent in a six-month period. Twenty animals are being observed for further studies of the anastomoic site and possible late carcinogenic activity of the monomer. The local histotoxicity of methyl-2-cyanoacrylate, the strong binding capacity, the abundance of scar tissue, and the distraction of the mucosa, as pointed out by several earlier investigators, were confirmed in this work. Also, it was strongly evident that the age of the glue has a significant influence on survival. The use of tissue adhesives as a substitute for standard suture technique or as a reinforcement of an inadequate suture line requires further study. Investigations designed for improving properties of these monomers appear warranted.

A foreign body (chicken bone) in the rectum causing extensive perirectal and scrotal abscess: report of a case.

A case of foreign-body perforation of the rectum with extensive necrotizing fasciitis is presented and the literature briefly reviewed. The peculiarity of the case was brought out because of the nature of the foreign body(chicken bone) and the extensiveness of the process. The increases risk of swallowing a foreign body if dentures are worn is pointed out.