Sex as a Biological Variable in Oral Diseases: Evidence and Future Prospects.

The interest of the scientific community on sex and gender differences in health and disease has increased substantially over the past 25 to 30 y as a result of a long process of events and policies in the biomedical field. This is crucial as compelling evidence from human and animal model studies has demonstrated that sex and gender influence health, molecular and cellular processes, and response and predisposition to disease. The present scoping review aims to provide a synthesis of sex differences in oral diseases, ranging from periodontal disease to orofacial pain conditions, from risk of caries development to apical periodontitis. Overall, findings from this review further support a role for sexual dimorphism influencing disease predisposition and/or progression in oral diseases. Of note, this review also highlights the lack of consideration of additional factors such as gender and other psychosocial and external factors potentially influencing oral health and disease. New conceptual frameworks capable of capturing multiple fundamental domains and measurements should be developed in clinical and preclinical studies to inform sex-based individualized preventive and treatment strategies.

The impact of sleep components, quality and patterns on glymphatic system functioning in healthy adults: A systematic review.

OBJECTIVE: The glymphatic system is thought to be responsible for waste clearance in the brain. As it is primarily active during sleep, different components of sleep, subjective sleep quality, and sleep patterns may contribute to glymphatic functioning. This systematic review aimed at exploring the effect of sleep components, sleep quality, and sleep patterns on outcomes associated with the glymphatic system in healthy adults. METHODS: PubMed®, Scopus, and Web of Science were searched for studies published in English until December 2021. Articles subjectively or objectively investigating sleep components (total sleep time, time in bed, sleep efficiency, sleep onset latency, wake-up after sleep onset, sleep stage, awakenings), sleep quality, or sleep pattern in healthy individuals, on outcomes associated with glymphatic system (levels of amyloid-ß, tau, α-synuclein; cerebrospinal fluid, perivascular spaces; apolipoprotein E) were selected. RESULTS: Out of 8359 records screened, 51 studies were included. Overall, contradictory findings were observed according to different sleep assessment method. The most frequently assessed sleep parameters were total sleep time, sleep quality, and sleep efficiency. No association was found between sleep efficiency and amyloid-ß, and between slow-wave activity and tau. Most of the studies did not find any correlation between total sleep time and amyloid-ß nor tau level. Opposing results correlated sleep quality with amyloid-ß and tau. CONCLUSIONS: This review highlighted inconsistent results across the studies; as such, the specific association between the glymphatic system and sleep parameters in healthy adults remains poorly understood. Due to the heterogeneity of sleep assessment methods and the self-reported data representing the majority of the observations, future studies with universal study design and sleep methodology in healthy individuals are advocated.

Evaluation of the protective effects of alpha-tocopherol and retinol against ochratoxin A cytotoxicity.

Ochratoxin A (OTA), a mycotoxin frequently present in food and feedstuffs, produces a wide range of toxic effects, including cell death via lipid peroxidation. In one human and four animal cell lines we determined the half lethal concentration (LC50) of OTA, its effect on reactive oxygen species (ROS) production, and its ability to induce cytochrome p450 activity. We also examined the protective effect of alpha-tocopherol and all-trans-retinol in the most sensitive cell lines (i.e. bovine mammary epithelia, for which LC50 was 0.8 microg/ml (24 h), and Madin Darby canine kidney, for which LC50 was 4.3 microg/ml (48 h)). Pre-incubation for 3 h with either antioxidant significantly (P<0.05) ameliorated the OTA-induced reduction in cell viability and significantly decreased (P<0.05) ROS production. These findings indicate that oxidative stress is an important factor in OTA cytotoxicity. Supplementation with antioxidant molecules may counteract the short-term toxicity of this mycotoxin.

Rumen-protected choline administration to transition cows: effects on milk production and vitamin E status.

We investigated the influence of rumen-protected choline (RPC) supplementation on milk production, lipid metabolism and vitamin E status in dairy cows receiving a silage-based diet. Twenty-six Italian Holstein multiparous cows were assigned by weight and average production in the previous lactation, to one of two groups: control (no RPC supplementation) and RPC (supplemented with 20 g/day rumen-protected choline chloride). Treatment began 14 days before expected calving and continued for 30 days after parturition. Choline administration significantly increased milk production during the first month of lactation and also the concentration (and total secretion) of choline in milk, but did not affect fat or protein concentrations in milk, or plasma levels of glucose, beta-hydroxybutyrate, cholesterol and non-esterified fatty acids (NEFA). However, around parturition, NEFA concentrations in plasma were lower in treated animals than in controls, suggesting improved lipid metabolism as a result of choline supplementation. Choline supplementation also increased alpha-tocopherol plasma concentrations, suggesting a novel aspect in dairy cows.

Hemoperitoneum in a continuous ambulatory peritoneal dialysis patient caused by a hepatocarcinoma treated with percutaneous embolization.

Hemoperitoneum is an infrequent but normally benign complication in continuous ambulatory peritoneal dialysis (CAPD) patients. It can occur at any time during peritoneal dialytic treatment. Hemoperitoneum is not associated with a specific disease and usually disappears spontaneously. In 20% of cases, however, hemoperitoneum is severe and requires specific investigation and emergency therapy. We report a case of hemoperitoneum in a 70-year-old, anti-hepatitic C virus-positive woman. After 48 months of CAPD treatment, a bloody peritoneal effluent developed, with severe anemia (hematocrit decreased from 30% to 20%). An abdominal computed tomography scan showed three hepatic lesions with signs of hepatic neoplasms; selective hepatic arteriography confirmed the diagnosis. Chemoembolization of the three lesions was performed, and hemoperitoneum disappeared within a few hours.

Direct effect of the correction of acidosis on plasma parathyroid hormone concentrations, calcium and phosphate in hemodialysis patients: a prospective study.

BACKGROUND: Metabolic acidosis contributes to renal osteodystrophy and together with hyperphosphatemia, hypocalcemia and altered vitamin D metabolism may result in increased levels of intact parathyroid hormone (iPTH) and metastatic calcifications. However, the impact of the correction of metabolic acidosis on iPTH levels and calcium-phosphate metabolism is still controversial. STUDY DESIGN: The effects of the correction of metabolic acidosis on serum concentrations of iPTH, calcium (Ca), phosphate (PO(4)) and alkaline phosphatase were prospectively studied. Twelve uremic patients on maintenance hemodialysis (HD) for 49 months (median; range 6-243 months) with serum bicarbonate levels < or =20 mmol/l were studied before and after 3 months of oral sodium bicarbonate supplementation. Predialysis serum bicarbonate, arterial pH, ionized calcium, plasma sodium, plasma potassium, serum creatinine, hemoglobin, K(t)/V, postdialysis body weight, predialysis systolic and diastolic blood pressure were also evaluated before and after correction. RESULTS: Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 to 24.4 +/- 1.2 mmol/l (p < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (p < 0.001). iPTH levels decreased significantly from 399 +/- 475 to 305 +/- 353 pg/ml (p = 0.026). No changes in total serum Ca, plasma PO(4), serum akaline phosphatase, K(t)/V, serum creatinine, hemoglobin, body weight, predialysis systolic and diastolic blood pressures were observed. iCa decreased significantly. CONCLUSIONS: Our study demonstrates that the correction of metabolic acidosis in chronic HD patients reduces iPTH concentrations in HD patients with secondary hyperparathyroidism possibly by a direct effect on iPTH secretion.

Distal arteriovenous fistulas in elderly hemodialysis patients.

Dialysis access procedures and complications are an important cause of morbidity and hospitalization for chronic hemodialysis patients. Subjects over 65 years old have a higher incidence of co-morbid factors (diabetes mellitus, atheros clerosis, neoplasms, heart failure), therefore the correct choice in terms of timing and type of permanent access is extremely important. As elbow fistulas are often complicated by heart failure and PTFE grafts have a higher risk of thrombosis, we decided to evaluate the success rate of distal fistula as primary dialysis access in elderly patients. We carried out a retrospective study to identify survival predictors and actual vascular network saving. Between January 1991 and September 2000, 277 vascular access procedures were performed on 198 elderly patients (age 65 or older). The first anastomosis was positioned as peripherally as possible. In cases of patients with poor peripheral vasculature or three co-morbid factors, vascular access was first created at the origin of radial artery (Toledo-Pereyra fistula). Survival (Kaplan - Meyer analysis) was significantly higher for Toledo-Pereyra fistulas compared to wrist and snuff-box ones, in spite of the presence of a high incidence of co-morbid factors. We conclude that Toledo-Pereyra fistula is an efficient primary choice in elderly patients.

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study.

BACKGROUND: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. STUDY DESIGN: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. RESULTS: Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 mmol/l to 24.4 +/- 1.2 mmol/l (P < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (P < 0.0001). Serum albumin increased from 34.9 +/- 2.1 g/l to 37.9 +/- 2.9 g/l (P < 0.01), while PCRn decreased from 1.11 +/- 0.17 g/kg/day to 1.03 +/- 0.17 g/kg/day (P < 0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. CONCLUSIONS: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentrations in HD patients. The correction of acidosis induces a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.

Feasibility of a long-term low-sodium diet in mild hypertension.

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.

Placental transfer, tissue distribution, and pharmacokinetics of cyclosporine in the pregnant rabbit.

The disposition of cyclosporine during pregnancy is described for the first time using the pregnant rabbit model. After a detailed kinetic study, in which a 5 mg/kg dose of cyclosporine was used, the apparent tissue-to-blood partition coefficients were determined at steady state in six pregnant rabbits after a two-step infusion of cyclosporine for 8 hr at a mean arterial blood concentration of 1.25 mg/liter, detected by HPLC. Muscle and fat were major drug deposits, and the maternal kidney--site of considerable side effects--accumulated the highest concentration of the drug. Spleen, mammary gland, liver, lung, heart, bile, and adrenal gland showed intermediate ability to accumulate the drug. The whole fetus accumulated little cyclosporine, and the drug was not detectable in maternal and fetal brains and in the amniotic fluid. At delivery, the mean cyclosporine concentration in fetal blood was 0.07 mg/liter, amounting to 6% of the mother's concentration. It would appear that diffusional resistance governs the transfer of cyclosporine into brain and fetus. Although caution obviously must be applied in extrapolating experimental data to clinical situations, the present findings do suggest that: a) exposure of the fetus to cyclosporine is low at a high maternal steady-state concentration; and b) caution should be applied in suggesting breastfeeding by these patients, since cyclosporine was found in a considerable amount in the mammary gland.

Cyclosporine pharmacokinetics in rats and interspecies comparison in dogs, rabbits, rats, and humans.

The pharmacokinetics of cyclosporine, a potent immunosuppressive agent, are described for rats given 5 mg/kg iv, measuring blood concentrations by a specific HPLC method. Cyclosporine followed first-order kinetics and blood concentrations vs. time data were adequately described by a three-compartment open model system. The mean half-life of the lambda 1 phase was 0.11 hr, that of the lambda 2 phase was 1.82 hr, and the half-life of the estimated lambda 3 phase was 23.79 hr. The mean apparent volume of distribution and Vss were 5.69 and 4.54 liters/kg, respectively. The mean blood total body clearance was 3.38 ml/min/kg. The literature was reviewed to obtain comparable data from other mammalian species, and satisfactory kinetic information was found for humans, dogs, and rabbits. Interspecies variants in physiological parameters and cyclosporine pharmacokinetics were considered and treated as a property and consequence of body size (allometry), nullifying anatomical and physiological differences between species. A relationship between pharmacokinetic time (a variable in terms of chronological time) and body weight was found. It is suggested that the metabolic capacity (based on liver weight) to eliminate cyclosporine is similar in humans, rabbits, and rats, whereas the dog showed a potentially double capacity to metabolize the drug. However, metabolic and pharmacodynamic studies are also needed to predict toxicity accurately among species.

Reversed-phase high-performance liquid chromatography determination of cyclosporin in human blood.

A high-performance liquid chromatographic (HPLC) method for determination of cyclosporin A (CyA) in blood, using cyclosporin D (CyD) as internal standard, is described. The method is specific, precise, reproducible, accurate, and isocratic, and it requires no derivatization. It is more rapid than previously described methods. Its detection limit is 25 ng/ml, suitable for quantitation of the drug at clinically observed concentrations. No interference was found by any of the other commonly coadministered drugs tested. Comparison of measurements in patients' blood with radioimmunoassay (RIA) results showed lower estimates by the chromatographic technique. Because measurements of the drug in blood banks spiked with pure CyA were similar with the two techniques, the nonspecificity of RIA, probably related to cyclosporin metabolites, was demonstrated. Because the chromatographic technique is simple, it should be preferred to RIA in therapeutic drug monitoring.

ATP as a marker of excitotoxin-induced nerve cell death in vivo.

In an attempt to find an marker for nerve cell death in vivo, the ATP content was measured in the rat dorsal hippocampus within hours or days following in the local injection of the excitotoxins quinolinic or kainic acid. Beginning or completed neuronal degeneration is accompanied by significant decreases in ATP levels. Selective blockade of the quinolinic acid-induced decrement in ATP content by D-(-) 2-amino-7-phosphonoheptanoic acid indicates that ATP measurements may of value for the rapid in vivo screening of the anti-neurotoxic properties of pharmacologically distinct excitatory amino acid receptor antagonists.