Role of nitric oxide in regulation of coronary blood flow during myocardial ischemia in dogs

Objectives. This study was undertaken to examine whether nitric oxide released in ischemic myocardium decreases the coronary vascular resistance and attenuates the severity of contractile and metabolic dysfunction.Background. Endothelium-derived relaxing factor, recently identified as nitric oxide, is a potent relaxant of coronary smooth muscle.Methods. The left anrterior descending coronary artery was perfused through an extracorporeal bypass tube placed in the carotid artery in 56 open chest dogs. After hemodynamic stabilization, we occluded this bypass tube to decrease coronary blood flow to one third of the control flow. Thereafter, we maintained a constant coronary perfusion pressure(40.9 ± 3.1mm Hg).Results. Under ischemic conditions, the coronary arteriovenous differences in nitrate and nitrite (end products of nitric oxide) increased (from 3.5 ± 0.4 [mean ± SEM] to 12.9 ± 2.1 μmol/liter, p < 0.01). ⁰-Monomethyl -arginine (3 μg/kg body weight per min, intracoronary) decreased the coronary arteriovenous differences in nitrate and nitrite (5.0 ± 0.9 μmol/liter, p < 0.05) and coronary blood flow (from 29.8 ± 0.5 to 18.1 ± 1.1 ml/100 g per min, p < 0.001). Fractional shortening (from 3.7 ± 1.0 to −1.3 ± 0.7%, p < 0.001) and lactate extraction ration (from −44.0 ± 4.1 to −59.2 ± 4.9%, p < 0.005) of the perfused area also decreased. These values were restored by the concomitant administration of -arginine. Blood flow to the endomyocardium was decreased relative to the epimyocardium. A reduction in coronary blood flow and worsening of myocardial contractile and metabolic functions due to the administration of ^G-monomethyl -arginine during ischemia were observed in denervated hearts. A reduction in coronary blood flow in ischemic myocardium was observed with the administration of ^W-nitro- -arginene methyl ester as well, although neither ^W-nitro- -arginine methyl ester nor ^G-monomethyl -arginine changed coronary blood flow and myocardial contractile and metabolic functions in the nonischemic myocardium. The cyclic guanosine monophosphate content of epicardial coronary artery increased due to myocardial ischemia; this increased was attenuated with ^G-monomethyl -arginine treatment.Conclusions. We conclude that endogenous nitric oxide predominantly decreases the coronary vascular resistance of ischemic endomyocardium, thereby improving myocardial contractility and metabolic function.     

Gout:A clinical overview and its association with cardiovascular diseases

Gout is a common disease caused by the deposition of monosodium urate(MSU) crystals in patients with hyperuricemia, and characterized by very painful recurrent acute attacks of arthritis. The gold standard for diagnosing gout is the identification of MSU crystals in synovial fluid by polarization light microscopy. Arthritis attacks can be treated with anti-inflammatory medications, such as non-steroidal anti-inflammatory drugs, colchicine, oral prednisone, or intra-articular or intramuscular glucocorticoids. To prevent gout uric acid lowering therapy with for example allopurinol can be prescribed. When gout is adequately treated, the prognosis is good. Unfortunately, the management of gout patients is often insufficient. Gout is associated with dietary factors, the use of diuretics, and several genetic factors. Comorbidities as hypertension, chronic kidney disease, cardiovascular diseases, the metabolic syndrome, diabetes, obesity, hyperlipidemia, and early menopause are associated with a higher prevalence of gout. Xanthine oxidase and chronic systemic inflammation seem to play an important role in the pathophysiology of the association between gout and cardiovascular diseases. To prevent cardiovascular diseases goutpatients must be early screened for cardiovascular risk factors.     

Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.     

Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A

In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD.     

Oral lichenoid drug eruptions

OBJECTIVES: To identify, from amongst drugs reported as causing lichenoid drug eruptions, those affecting the oral mucous membranes and to review the clinical, histo-logical and immunological features of such oral lichenoid drug eruptions in comparison to oral lichen planus, amalgam contact lesions and lichen planus-like eruption in graft-versus-host disease (GVHD).
DATA SOURCES: Ovid® Medline data searches on CD-Rom were carried out for the years 1966–1996 to identify reports of oral lichenoid drug eruptions and their clinical, histological and immunological featureS. Articles retrieved were examined for further appropriate references in the period 1940–1996.
DATA EXTRACTION AND SYNTHESIS: Each paper was critically examined for evidence of a clinically verifiable lichenoid drug eruption affecting the oral mucous membranes and the effects of subsequent drug withdrawal. Available clinical, histological and immunological features were recorded. The papers examined were too diverse in nature to permit a structured criticism. The extracted data have been tabulated where appropriate.
CONCLUSIONS: The reports of oral lichenoid drug eruptions are considerably fewer than those of cutaneous eruptions and fewer drugs have been reported as causing oral rather than cutaneous lichenoid eruptionS. Histology and immunology cannot be used reliably to differentiate lichenoid drug eruptions from idiopathic lichen planus, amalgam contact lesions and lichen planus-like eruption in GVHD. Lichenoid drug eruptions may also show some histological characteristics of oral discoid lupus erythematosuS. An accepted protocol agreed by a number of international centres would permit the gathering of substantial information on LDE and could lead to a greater understanding of the mechanisms involved.     

Rosacea – global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group

Background The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. Objectives The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. Methods The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. Results New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein‐5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein‐5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy – the triad of rosacea care – that integrates patient education including psychological and social aspects, skin care with dermo‐cosmetics as well as drug‐ and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. Conclusion The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence‐based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.     

Burn depth assessment by dual-wavelength light emitting diodes-excited photoacoustic imaging in rats

Accurate burn depth assessment is crucial to determine treatment plans for burn patients. We have previously proposed a method for performing burn depth assessments based on photoacoustic (PA) imaging, and we have demonstrated the validity of this method, which allows the successful detection of PA signals originating from the blood under the bloodless burned tissue, using rat burn models. Based on these findings, we started a clinical study in which we faced two technical issues: (1) When the burn depth was shallow, PA signals due to skin contamination and/or melanin in the epidermis (surface signals) could not be distinguished from PA signals originating from the blood in the dermis; (2) the size of the system was too large. To solve these issues, we propose a burn depth diagnosis based on dual-wavelength light emitting diodes (LEDs)-excited PA imaging. The use of LEDs rendered the system compact compared to the previous one that used a conventional solid-state laser. We replicated human burned skin by applying a titrated synthetic melanin solution onto the wound surface in albino rat burn models and measured their burn depths by PA excitation at 690 and 850 nm, where melanin and haemoglobin show greatly different absorption coefficients. As a result, the surface signals were eliminated by subtracting the PA signals at 690 nm from those at 850 nm. The resultant estimated burn depths were strongly correlated with the histological assessment results. The validity of the proposed method was also examined using a burn model of rats with real melanin.     

A challenge of deep-learning-based object detection for hair follicle dataset

Background

Deep-learning object detection has been applied in various industries, including healthcare, to address hair loss.

Methods

In this paper, YOLOv5 object detection algorithm was used to detect hair follicles in a small and specific image dataset collected using a specialized camera on the scalp of individuals with different ages, regions, and genders. The performance of YOLOv5 was compared with other popular object detection models.

Results

YOLOv5 performed well in the detection of hair follicles, and the follicles were classified into five classes based on the number of hairs and the type of hair contained. In single-class object detection experiments, a smaller batch size and the smallest YOLOv5s model achieved the best results, with an map of 0.8151. In multiclass object detection experiments, the larger YOLOv5l model was able to achieve the best results, and batch size affected the result of model training.

Conclusion

YOLOv5 is a promising algorithm for detecting hair follicles in a small and specific image dataset, and its performance is comparable to other popular object detection models. However, the challenges of small-scale data and sample imbalance need to be addressed to improve the performance of target detection algorithms.     

Handheld microfocused ultrasound device for facial lifting: A preliminary study of ULTIGHT

Objective

Although focused ultrasound modalities have achieved positive clinical results in noninvasive skin rejuvenation, they presented various side effects and particularly severe pain during treatment. This study introduces a microfocused ultrasound (MFU) device, ULTIGHT, to overcome the severe pain issue, providing quasi-facial lifting.

Materials and Methods

Transducer surface was imaged with a scanning electron microscope. The energies of four treatment cartridges were measured using an ultrasound power meter. In vitro experiments were performed to quantitatively evaluate the MFU thermal zones (MFUTZs) and treatment line (TL) of 10 MFUTZs. Ex vivo experiments were performed to evaluate the MFUTZs and temperature rise in tissue. Clinical trials using eight volunteers were performed to qualitatively evaluate facial lifting.

Results

The MFU transducer clearly showed a smooth and no air gap surface. ULTIGHT produced 10 discrete MFUTZs in a TL of length 10 mm. In ex vivo tissue, discrete linear MFUTZs were clearly observed at lower number of TLs; however, they started to aggregate at higher number of TLs. The temperature rise was linearly increased as a function of the number of treatments. A single MFUTZ resulted in a temperature rise of 3°C–10°C that could cause hyperthermia for body temperature. In the clinical trials, the volunteers showed quasi-facial lifting right after treatment on the lower facial region.

Conclusions

ULTIGHT provides relatively low energy, which may be advantageous or disadvantageous depending on clinical applications. Additionally, it has the advantage of being pain-free even without anesthetic during treatment, providing quasi-facial lifting right after treatment.