MicroRNA-155 (miR-155) as an accurate biomarker of periodontal status and coronary heart disease severity: a case-control study.

BACKGROUND: Increasing evidence supports associations between periodontal disease and coronary heart disease (CHD). This case-control study evaluated whether inflammatory regulator, microRNA-155 (miR-155), could be utilised as a biomarker of periodontitis and/or CHD. METHODS: Of 120 participants, 30 patients had clinically healthy periodontium (controls, C), 30 patients had generalized periodontitis (P), 30 patients had CHD and clinically healthy periodontium (AS-C); and 30 patients had CHD with generalized periodontitis (AS-P). Patient demographic and periodontal characteristics (plaque index, bleeding on probing, probing pocket depth and clinical attachment loss), were collected. Patient whole blood and saliva levels of miR-155 and pro-inflammatory cytokine (interleukin-1ß), were quantified by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). One-way ANOVA with post-hoc Tukey test was used to determine differences among the four groups. Chi Square test was used for participant gender comparisons. Pearson correlation tests and multiple linear regression analyses were used to assess associations between the demographic and clinical variables analysed, versus IL-1ß and miR-155 levels. miR-155 and IL-1ß accuracy in differentiating healthy versus other patient groups were analysed using receiver operating characteristic (ROC) curves, by calculating area under the curve (AUC) values and sensitivity and specificity cut-off points using Youden's index. Statistical tests of sensitivity and specificity were conducted using the McNemar test. RESULTS: Whole blood miR-155 levels were elevated in periodontitis/non-periodontitis patients with CHD (AS-P, AS-C), and periodontitis patients alone (P) (p < 0.001). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses confirmed miR-155 accuracy in discriminating P, AS-C and AS-P groups (AUC 0.6861-0.9944, p < 0.0001-0.05), coupled with high sensitivity (76.7-100.0%), specificity (53.3-96.7%) and cut-off points (> 0.955- > 2.915 a.u.; p < 0.0001). miR-155 levels further distinguished between CHD (AS-C, AS-P) and periodontitis (P) patients (AUC ≥ 0.8378, sensitivity ≥ 88.7%, specificity ≥ 73.3%, cut-off > 2.82 a.u; p < 0.0001), and between AS-C and AS-P patients (AUC 0.7578, sensitivity 80.0%, specificity 50.0%, cut-off > 7.065 a.u; p < 0.001). Subsequent analyses identified positive correlations between miR-155 and the various patient demographics, salivary interleukin-1ß and periodontal parameters assessed. CONCLUSIONS: This study advocates miR-155 as an accurate diagnostic/prognostic biomarker of periodontitis and/or CHD severity, thereby improving detection and treatment for both conditions.

Effects of Oral Sodium Bicarbonate Supplementation on Protein Metabolism and Inflammation in Iraqi Hemodialysis Patients: An Open-Label Randomized Controlled Trial.

Background: The effect of correcting metabolic acidosis on protein metabolism in hemodialysis patients is controversial. Objectives: To study the effects of oral sodium bicarbonate on protein metabolism and markers of inflammation in acidotic hemodialysis patients. Patients and Methods. An open-label randomized controlled trial was conducted at a single center. Sixty-six clinically stable adult hemodialysis patients were recruited with an average predialysis serum bicarbonate level of <22 mmol/l and a dialysate bicarbonate concentration of 35 mmol/l. Forty-nine participants have completed the study. Oral sodium bicarbonate tablets of 500 mg were given daily in the intervention group (n = 25) for 12 weeks versus the standard of care in the control group (n = 24). Outcomes compared intervention versus nonintervention in both groups at equivalent time points (0 and 3 months). The clinical data, anthropometry, dialysis adequacy, albumin, normalized protein catabolism rate, blood gas analysis, and bicarbonate were recorded at 0 and 3 months. In addition, muscle mass and handgrip strength were measured. Finally, IL-6 as a marker of inflammation was measured at randomization and three months. Results: Serum bicarbonate and pH increased significantly from 17.57 ± 3.34 mmol/L to 20.69 ± 2.54 mmol/L and from 7.26 ± 0.06 to 7.34 ± 0.04, respectively (p < 0.0001). Serum albumin was significantly higher in the intervention group at three months than in the control group, 4.11 ± 0.45 vs. 3.79 ± 0.47 (p value 0.011). Serum potassium significantly decreased in the intervention group at three months compared to the control group, 5.00 ± 0.43 mEq/l vs. 5.33 ± 0.63 mEq/l (p value 0.03). Muscle strength expressed as handgrip has improved significantly in the intervention group at three months compared to the control group, 45.01 ± 19.19 vs. 33.93 ± 15.06 (p value 0.03). The IL-6 values were less in the intervention group at 3 months with a p value of 0.01. The interdialytic weight of the intervention group at three months was 2.42 ± 0.64 compared to the 2.20 ± 1.14 control group, but this did not reach statistical significance (p value of 0.4). The composite of (albumin + nPCR) at three months was achieved in 59.18% of the intervention group compared to 14.28% with a p value of 0.01. Conclusions: Correcting metabolic acidosis in hemodialysis patients improved serum albumin and nPCR without hypokalemia or significant interdialytic weight gain. This was particularly evident in patients with minimal inflammation with low IL-6 values.

Nanocomposite Bioprinting for Tissue Engineering Applications.

Bioprinting aims to provide new avenues for regenerating damaged human tissues through the controlled printing of live cells and biocompatible materials that can function therapeutically. Polymeric hydrogels are commonly investigated ink materials for 3D and 4D bioprinting applications, as they can contain intrinsic properties relative to those of the native tissue extracellular matrix and can be printed to produce scaffolds of hierarchical organization. The incorporation of nanoscale material additives, such as nanoparticles, to the bulk of inks, has allowed for significant tunability of the mechanical, biological, structural, and physicochemical material properties during and after printing. The modulatory and biological effects of nanoparticles as bioink additives can derive from their shape, size, surface chemistry, concentration, and/or material source, making many configurations of nanoparticle additives of high interest to be thoroughly investigated for the improved design of bioactive tissue engineering constructs. This paper aims to review the incorporation of nanoparticles, as well as other nanoscale additive materials, to printable bioinks for tissue engineering applications, specifically bone, cartilage, dental, and cardiovascular tissues. An overview of the various bioinks and their classifications will be discussed with emphasis on cellular and mechanical material interactions, as well the various bioink formulation methodologies for 3D and 4D bioprinting techniques. The current advances and limitations within the field will be highlighted.

In vitro and in vivo evaluation of the antiangiogenic activities of Trigonella foenum-graecum extracts

Objective To assess the antiangiogenic activity of fenugreek. Methods Different fractions of fenugreek crude extracts were prepared and their antiangiogenic properties were assessed using the ex vivo rat aortic ring assay and in vivo chicken embryo chorioallantoic membrane (CAM) assay. They were investigated for their direct cytotoxic activity in the MCF7 cells using the MTT assay. Results The ethanol extract showed 100% inhibition of blood vessel outgrowth from primary tissue explants in the rat aortic ring assay at a concentration of 100 μg/mL while the other extracts did not show significant antiangiogenic activity. The ethanol extract was therefore investigated at varying concentrations and exhibited a significant dose dependent effect. The CAM assay coincided with the results of the aortic ring assay as ethanol extract showed a significant inhibition of formation of new blood vessels. The extracts only showed anti-proliferative activity at the highest concentration of 400 μg/mL towards MCF7 breast cancer cell lines in the MTT assay. Conclusions Findings of the both assays confirmed that the ethanol extract inhibited vascularization significantly. Further studies on the ethanol extract would be beneficial in isolating the active ingredient responsible for the inhibition.

[Uremic pruritus]. / Il prurito uremico.

Among the various dermatologic abnormalities that can be associated with advanced chronic renal failure and dialysis therapy, pruritus is certainly the most disturbing disorder. Pruritus is an unpleasant, vexing sensation that provokes an intense desire to scratch. In the past the pruritus was considered from the neurophysiologic point of view as a submodality of pain, but more recent research showed that pain and pruritus are sensations which are carried through different populations of primary sensory neurons. The causes of pruritus in uremic patients are still unknown: xerosis, intradermic microprecipitation of divalent ions, hyperparathyroidism, peripheral neuropathy, allergic reactions and hypersensitivity, histamine and others have been considered as pathogenetic factors. The uncertainty on the causes is in part responsible for the different approach and results, unsatisfactory in many cases. In this paper we will review the neurophysiology, the pathogenesis and the possible therapeutic approaches to uremic pruritus.

Congenital muscular dystrophy associated with familial junctional epidermolysis bullosa letalis.

A 20-year-old patient was born with epidermolysis bullosa and a severe, slowly progressive muscle disease. Skin biopsy demonstrated junctional epidermolysis bullosa. Muscle biopsy demonstrated degenerative changes with increase in connective tissue, fibre size variability, rods and cytoplasmic bodies, central nuclei. In muscle biopsy dystrophin, chondroitin unsulphate, chondroitin 4-sulphate, chondroitin 6-sulphate, heparan sulphate, collagen III, collagen IV and VI, laminin, and fibronectin were normally distributed. This is the first report of the association of a form of congenital muscular dystrophy with junctional epidermolysis bullosa and, together with the previous reports of muscle involvement in epidermolysis bullosa simplex and dystrophica, it suggests the existence of a syndrome characterized by the contemporaneous presence of skin and muscle involvement.

[Ulcerative herpes simplex as the first manifestation of AIDS]. / Herpes simplex ulcerativo come prima manifestazione di AIDS.

We present the case of an ulcerative lesion of the nasal mucous membrane and of the cutis surrounding the nose, starting six months ago, in a 26 year-old woman. From the histological picture a necrotic Herpes-virus infection was diagnosed. This suggested the existence of a deficiency of cell-mediated immunity. In fact a selective quantitative defect in the helper/inducer subset of T lymphocytes, as observed in AIDS, was noticed. HIV infection was confirmed by the ELISA test and the Western Blot test. Viral cultures grew HSV I from the skin lesion, which rapidly recovered after treatment with Acyclovir. We emphasize the absence of other signs and symptoms that could make us suspect an HIV infection and the rarity in the literature of the occurrence of HSV infections in that particular location as an initial manifestation of AIDS.

[Clinical evaluation of josamycin in the treatment of acne]. / Valutazione clinica della josamicina nella terapia dell'acne.

The efficacy of josamycin in the treatment of inflammatory acne has been evaluated in 39 patients. Josamycin was orally administered to the patients as a single 500 mg daily dose for two months, but the patients with the most severe lesions received an initial treatment of 1 g for a maximum of 20 days. All subjects received josamycin in combination with other antiacne drugs mostly benzoyl peroxide ointment. The treatment induced a significant regression of the number and the severity of the lesions scored according to Plewig-Kligman's classification. At the end of the treatment a positive effect was observed for 92% of the subjects, independently of the variety and the degree of the severity of the disease. According to the patients' judgments josamycin was an effective treatment (92.3%) and more effective that the previously prescribed drugs (95%). Only 1 patient reported the occurrence of a side effect (mild gastric discomfort). Josamycin showed in this study to be an effective and safe drug for the treatment of inflammatory acne.

Papular xanthoma. Clinical, histological and ultrastructural study.

The 5th case of papular xanthoma is reported. This entity can be differentiated on the basis of clinical and histological features: normolipidemic, nonconfluent, eruptive xanthomas located on the face, trunk and mucous membranes with no internal involvement. Histologically there are foamy cells and Touton giant cells without an inflammatory or histiocytic component. Electron microscopy shows macrophages packed with free lipidic vacuoles and lacking specific markers.

Hepatoerythropoietic porphyria.

A patient with hepatoerythropoietic porphyria had typical cutaneous manifestations: photosensitivity with blistering and mild scarring, and hypertrichosis. Biochemically elevated levels of protoporphyrins in erythrocytes, uroporphyrins in urine, and coproporphyrins in feces are markers of this form of porphyria. A family study confirmed that he was homozygous for a defect of uroporphyrinogen decarboxylase. A trial with hydroxychloroquine produced no improvement.

Dermatitis in a rubber tyre factory.

An outbreak of occupational dermatitis in a rubber tyre factory is reported. An unusual clinical picture was recognized. Patch tests revealed a high sensitization rate to the MBT derivative used: 2-(2'-4'dinitrophenylthio)benzothiazole. Since tests with MBT mix and dinitrophenol were negative; sensitization to a contaminant was suspected. DNCB was traced as the substance responsible.

Echocardiography of the pericardium in pregnancy.

Echocardiography is a simple, accurate, and noninvasive technique for the study of the pericardium. Twenty-one normal pregnant women in their third trimester were examined with the Smith-Kline Ekoline 20 Ultrasonoscope. Twelve (57.1%) had normal echocardiography, and nine (42.9%) had pericardial effusion: four mild, three moderate, and two large in amount. There was no correlation between the amount of pericardial effusion and the red blood cell and white blood cell counts, hemoglobin level, total serum protein, serum albumin level, or albumin/globulin ratio. One patient with moderate effusion was followed for 50 days after delivery, by which time the effusion had resolved completely.

Sea-blue histiocyte syndrome with cutaneous involvement. Case report with ultrastructural findings.

A patient with infiltration of the skin resulting in eyelid swelling and facial nodules was recognized as a case of sea-blue histiocyte syndrome with cutaneous involvement. Typical sea-blue histiocytes were found in the skin and confirmation was provided by electron microscopy. Hepatosplenomegaly, lung infiltrates and bone marrow involvement were the other symptoms. The relationship between sea-blue histiocyte syndrome and adult Niemann-Pick disease is also discussed.

Recurrent digital fibromatosis of childhood. An ultrastructural and immunohistochemical study of two cases.

Two cases of recurrent digital fibromatosis of childhood were studied by electron microscopy and immunohistochemistry, using rabbit anti-actin antisera. The tumor cells were typical myofibroblasts, containing inclusion bodies and bundles of microfilaments. Immunohistochemistry showed the presence of actin in these cells, thus proving the myofibroblastic nature of the tumors. Inclusions were negative or showed a weak annular positivity. A possible explanation of these findings is discussed.

Gross pathology and scanning electron microscopy of pilomatricoma.

We have examined gross specimens of pilomatricomas, divided in half after surgical excision and have found a peculiar gross appearance that has enabled us to arrive at a correct diagnosis. The macroscopic structure of the tumor appears to conform to the scanning electron microscopic picture.