Efficacy and safety of oral porcine relaxin (pRLX) in adjunct to physical exercise in the treatment of peripheral arterial disease (PAD)

Introduction PAD medical therapy has a number of limitations. RLX showed promises in experimental model mainly through NO release. Our study is the first to evaluate the efficacy and safety of RLX in PAD. Materials-Methods eligible PAD La fontaine IIa-IIb patients were randomized in 2 groups. Group A was treated with physical therapy plus oral pRLX, 20 ug b.i.d for 12 weeks, group B received physical therapy alone. Pain Free Walking Distance (PFWD) and Maximum Walking Distance (MWD) at 3 and 12 wks and at follow up 3 months after treatment interruption were performed. Results The percentage increases of PFWD in group B were 23±9, 65±17, and 35±4 respectively at 3 and at 12 weeks. and 3 months after termination. In Group A showed significantly higher percentage increases: 74±16 p<0.01, 168±28 p<0.001, and 122±15 p<0.001 at the corresponding time points. The percentage increases of MWD in the B group were 29±7, 55±10 and 54±8 at the above time points, while in the A group were 55±10 p<0.001, and 99±12 p<0.001. The RLX patients referred a better physical and mental status. No adverse events during or after the treatment were recorded. Comment-RLX resulted very effective in PAD. Our results may suggest that the observed functional benefits should come not only from hemodynamic improvement but also from positive vascular remodeling

Efficacy of Relaxin on functional recovery of post stroke patients

Background. Relaxin is a peptide hormone that exerts specific effects on cardiovascular system and human brain, leading to the hypothesis that this hormone may play a protective role against CVD and integration and modulation of behavioral activation. We aimed to demonstrate the efficacy of Relaxin on functional recovery of post-stroke patients. Methods. Patients admitted within a Rehabilitation Unit suffering from stroke have been evaluated. Patients have been randomized to RLX (40 mcg/d) plus rehabilitation vs a control group that underwent only rehabilitation. A preliminary analysis of 36 patients at 20 and 40 days was made using the mRS for global function, the Functional Independent Measure (FIM) for daily activity and Trail Making Test (TMT) for cognitive function. Results. Eighteen patients (age 72 (64-79), M 56%) randomized to RLX plus rehabilitation were compared to 18 patients (age 68 (64-78), M 50%) that underwent only rehabilitation. There was no difference between the two groups in terms of risk factors, stroke syndromes and etiology. At admission the two groups showed the same characteristics in terms of functional aspects (mRS, FIM; p ns) and cognitive function (TMT; p ns). After 20 days (T1) the treatment group (RLX+rehabilitation) showed no differences between the two groups (FIM 78 vs 69; p ns), while after 40 days (T2) patients treated with RLX+R showed an excellent recovery (FIM 96 vs 75; p0.001). In terms of cognitive function patients RLX+R revealed a better performance at T1 ( TMT 3.5 vs 2; p 0.002) and still better at T2 (TMT 4 vs 2; p 0.001). These results have been confirmed in terms of global function both at T1 (mRS 2.5 vs 3; p0.001) and T2 (mRS 2 vs 3; p <0.001) . Conclusion. Relaxin showed in this analysis a positive effects on stroke patient’s recovery, thus offering the broad therapeutic potential role of RLX as new drug in post-stroke patients

Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

BACKGROUND: In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD). Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH), ischemic heart disease, heart failure, peripheral vascular disease (PVD), diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema) and severity (mild and severe diseases) were determined by clinical and functional parameters. METHODS: A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide %) and sputum characteristics. Comorbidities were assessed by objective medical records. RESULTS: Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively). IAH prevailed significantly in predominant airway disease, osteoporosis prevailed significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. CONCLUSION: Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and score COPD allows these results to be translated easily into daily clinical practice

Effects of relaxin on the microvasculature of mouse mammary gland

The effects of RLX on the microvasculature of the mouse mammary gland are reported. RLX (pure porcine standard NIH-RXN-P1) at a dose of 3 GPU was administered subcutaneously to virgin adult mice ovariectomized 12 days before. The mammary glands were removed 18-20 h after RLX injection and their examination by light microscopy did not reveal any substantial growth-response to the hormone . Histology and morphometry indicated striking dilation of microvessels, especially capillaries. and electron microscopy revealed an increase in the micropinocytotic vesicles, thus suggesting enhanced transendothelial transport of substances. Such phenomena, which were independent of a release of granules by mast cells, may represent an important component of the mammotrophic action of RLX

Glottis Closure Influences Tracheal Size Changes in Inspiratory and Expiratory CT in Patients with COPD

Rationale and Objectives: The opened or closed status of the glottis might influence tracheal size changes in inspiratory and expiratory computed tomography (CT) scans. We investigated if the glottis status makes the tracheal collapse differently correlate with lung volume difference between inspiratory and expiratory CT scans. Materials and Methods: Forty patients with chronic obstructive pulmonary disease whose glottis was included in the acquired scanned volume for lung CT were divided into two groups: 16 patients with the glottis closed in both inspiratory and expiratory CT, and 24 patients with the glottis open in at least one CT acquisition. Lung inspiratory (Vinsp) and expiratory (Vexp) volumes were automatically computed and lung \u3b4V was calculated using the following formula: (Vinsp - Vexp)/Vinsp 7 100. Two radiologists manually measured the anteroposterior diameter and cross-sectional area of the trachea 1 cm above the aortic arch and 1 cm above the carina. Tracheal collapse was then calculated and correlated with lung \u3b4V. Results: In the 40 patients, the correlations between tracheal \u3b4anteroposterior diameter and \u3b4cross-sectional area at each level and lung \u3b4V ranged between 0.68 and 0.74 (\u3c1) at Spearman rank correlation test. However, in the closed glottis group, the correlations were higher for all measures at the two levels (\u3c1 range: 0.84-0.90), whereas in the open glottis group, correlations were low and not statistically significant (\u3c1 range: 0.29-0.34) at the upper level, and moderate at the lower level (\u3c1 range: 0.51-0.55). Conclusions: A closed or open glottis influences the tracheal size change in inspiratory and expiratory CT scans. With closed glottis, the tracheal collapse shows a stronger correlation with the lung volume difference between inspiratory and expiratory CT scans