Dietary Vitamin D Mitigates Coronavirus-Induced Lung Inflammation and Damage in Mice.

The COVID-19 pandemic caused by the SARS-CoV-2 (ß-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid hormone best known for its role in bone health, exhibits immunomodulatory effects in certain viral infections. Here, we have shown that bioactive vitamin D (calcitriol) limits in vitro replication of SARS-CoV-2 and murine coronaviruses MHV-3 and MHV-A59. Comparative studies involving wild-type mice intranasally infected with MHV-3, a model for studying ß-CoV respiratory infections, confirmed the protective effect of vitamin D in vivo. Accordingly, mice fed a standard diet rapidly succumbed to MHV-3 infection, whereas those on a vitamin D-rich diet (10,000 IU of Vitamin D3/kg) displayed increased resistance to acute respiratory damage and systemic complications. Consistent with these findings, the vitamin D-supplemented group exhibited lower viral titers in their lungs and reduced levels of TNF, IL-6, IL-1ß, and IFN-γ, alongside an enhanced type I interferon response. Altogether, our findings suggest vitamin D supplementation ameliorates ß-CoV-triggered respiratory illness and systemic complications in mice, likely via modulation of the host's immune response to the virus.

Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.

Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.

BACKGROUND: Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect. METHODS: The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2µg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of ß-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws. RESULTS: Intraplantar injection of kahweol (40 and 80µg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80µg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100µg/paw) prevented action of kahweol (80µg/paw) and the aminopeptidases inhibitor bestatin (400µg/paw) potentiated the antinociceptive effect of kahweol (40µg/paw). Furthermore, kahweol treatment increased the intensity of ß-endorphin immunoreactivity in the epithelium of rat paws. CONCLUSIONS: The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

Lithothamnion muelleri treatment ameliorates inflammatory and hypernociceptive responses in antigen-induced arthritis in mice.

Rheumatoid Arthritis (RA) is a chronic disease characterized by persistent inflammation and pain. Alternative therapies to reduce these symptoms are needed. Marine algae are valuable sources of diverse bioactive compounds. Lithothamnion muelleri (Hapalidiaceae) is a marine algae with anti-inflammatory, antitumor, and immunomodulatory properties. Here, we investigated the potential anti-inflammatory and analgesic activities of L. muelleri in a murine model of antigen-induced arthritis (AIA) in mice. Our results demonstrate that treatment with L. muelleri prevented inflammation and hypernociception in arthritic mice. Mechanistically, the crude extract and the polysaccharide-rich fractions of L. muelleri may act impairing the production of the chemokines CXCL1 and CXCL2, and consequently inhibit neutrophil influx to the knee joint by dampening the adhesion step of leukocyte recruitment in the knee microvessels. Altogether our results suggest that treatment with L.muelleri has a potential therapeutic application in arthritis treatment.

Sacral neuromodulation for neurogenic non-obstructive urinary retention in incomplete spinal cord patients: a ten-year follow-up single-centre experience.

OBJECTIVE: To determine the success rate of percutaneous first stage of sacral neuromodulation (SNM) and the efficacy and safety of permanent SNM for incomplete spinal cord lesion (SCL) patients suffering from chronic neurogenic non-obstructive urinary retention (N-NOR). METHOD: From January 2003 to December 2012, 85 individuals underwent the percutaneous first stage of SNM. Subsequently, only responders who reached a concomitant reduction by at least 50% of volume per catheterization and in the number of catheterizations per day comparing their 7-day voiding diaries at baseline underwent permanent SNM. Final follow-up was conducted by April 2013. RESULTS: Thirty-six individuals responded to percutaneous first stage of SNM. Post-surgery urodynamics documented all patients experiencing first sensation of bladder filling. A statistically significant increase in Qmax ml per sec and decrease in post-voiding residual urine per ml were documented. (P<0.01). First sensation of bladder filling at baseline represented a statistically significant parameter for the success of the first stage SNM (P<0.05). Eleven out of 34 patients at follow-ups were 'inconstant responders' because they returned to similar baseline voiding symptoms, but responded again with an implant on the controlateral S3 sacral root. Two failed twice and responded once again after an S4 sacral root implant. All but one failure occurred more than 3 years after the previous implant. Other drawbacks were resolved telemetrically. CONCLUSIONS: Research is needed to increase the success rate of the first stage SNM on incomplete SCL patients with N-NOR. Permanent SNM is highly efficacious in the medium follow-up.

Mechanisms of the anti-inflammatory actions of the angiotensin type 1 receptor antagonist losartan in experimental models of arthritis.

Angiotensin (Ang) II and its AT1 receptors have been implicated in the pathogenesis of rheumatoid arthritis. Activation of the counter-regulatory Ang-(1-7)-Mas receptor axis may contribute to some of the effects of AT1 receptor blockers (ARBs). In this study, we have used losartan, an ARB, to investigate the role of and the mechanisms by which AT1 receptors participated in two experimental models of arthritis: antigen-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Treatment with losartan decreased neutrophil recruitment, hypernociception and the production of TNF-α, IL-1ß and chemokine (C-X-C motif) ligand 1 in mice subjected to AIA. Histopathological analysis showed significant reduction of tissue injury and inflammation and decreased proteoglycan loss. In addition to decreasing cytokine production, losartan directly reduced leukocyte rolling and adhesion. Anti-inflammatory effects of losartan were not associated to Mas receptor activation and/or Ang-(1-7) production. Anti-inflammatory effects were reproduced in rats subjected to AdIA. This study shows that ARBs have potent anti-inflammatory effects in animal models of arthritis. Mechanistically, reduction of leukocyte accumulation and of joint damage was associated with local inhibition of cytokine production and direct inhibition of leukocyte-endothelium interactions. The anti-inflammatory actions of losartan were accompanied by functional improvement of the joint, as seen by reduced joint hypernociception. These findings support the use of ARBs for the treatment of human arthritis and provide potential mechanisms for the anti-inflammatory actions of these compounds.

Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention.

OBJECTIVES: To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary retention (N-NOR). METHODS: In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM. RESULTS: Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months. CONCLUSION: A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.

Clinical efficacy of intravesical electrostimulation on incomplete spinal cord patients suffering from chronic neurogenic non-obstructive retention: a 15-year single centre retrospective study.

OBJECTIVE: To evaluate the clinical and urodynamic impact of intravesical electrostimulation (IVES) on incomplete spinal cord injury (SCI) patients suffering from chronic neurogenic non-obstructive urinary retention (N-NOR). METHODS: One-hundred and two patients underwent at least 28 consecutive daily IVES sessions because objective evidence of detrusor acontractility instead of hypocontractility was detected. Diary entries written at various stages by each patient were compared (7 days before the IVES cycle, 15-21 days into the cycle and 7 days before its end). Responders were patients with a mean 50% reduction in both the number of daily catheterizations and post-void residual urine. Responders underwent further urodynamics at the end of the IVES cycle; patients experiencing first sensation of bladder filling, and the mean volume of first sensation of bladder filling per ml, Qmax ml s(-1), among others, were evaluated. Nineteen individuals who repeated another IVES round were included in this study. RESULTS: Thirty-eight subjects (37.2%) responded to IVES and of those, 83.3% recovered the first sensation of bladder filling after the IVES round. Nineteen responders repeated IVES within 1 year, owing to loss of efficacy. They obtained similar voiding symptoms improvement and urodynamic results as after the first IVES cycle. A timespan of <2 years from SCI to IVES, and the presence of first sensation of bladder filling at baseline represented significant predictive parameters for IVES success (P<0.05) using χ(2)-test. CONCLUSIONS: IVES represents a possible therapeutic option for incomplete SCI patients with N-NOR.

[Alternative treatment of benign prostatic hypertrophy]. / Il trattamento alternativo della ipertrofia prostatica benigna.

In our study we propose to find an alternative to surgery management of IPB usable in DH regime with current instrumentation or with new technology from physics. We retrospectively reviewed techniques commonly mentioned in the literature to value benefits about cost, comfort, outcomes, and, at the same time, we stress disadvantages regarding each of these. TUI is economical, can be done in a few minutes, involves minimum bleeding, but can't be utilized in III lobe prostate and it doesn't provide material for histological tests. TUBT, feasible with light patient sedation, provides not satisfying results. Hyperthermia is necessary in selected cases. TULIP must be effected in anesthesia, needs complicated and expensive instrumentation, and it isn't practicable in III lobe prostate. Urethral stent application is expensive and not satisfactory in large size and III lobe prostate. The outcomes we obtained with TUI are similar to TUR; TUBT obtains good symptomatological results only in 20% of cases at 12 months. Hyperthermia and TULIP obtain an improvement in urinary flow rate from 20 to 60% and 50% respectively. Stent application provides good results. We think that the most modern, effective and economical alternative to the surgery of prostate adenoma is endoscopic surgery in TUI model.