Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Improving the iron status of school children through a school noon meal programme with meals prepared using a multiple micronutrient-fortified salt in Tamil Nadu, India.

BACKGROUND AND OBJECTIVES: To improve the iron status of school children through noon meals prepared using a multiple micronutrient-fortified salt. METHODS AND STUDY DESIGN: Children from a randomly selected school who consumed (intervention) and did not consume (reference) a noon meal prepared using a multiple micronutrient- fortified salt were studied over 1 year. A pre-post-test design for children aged 5-17years in reference (n=100) and intervention (n=128) groups was used. Levels of serum ferritin, soluble transferrin receptor (sTfR), alpha glycoprotein (AGP), and C-reactive protein (CRP) were assessed at baseline and at 1 year. In a subsample, urinary iodine was assessed. RESULTS: sTfR decreased in the intervention group (-0.80 mg/L) but increased in the reference group (0.47 mg/L) at 1 year (p=0.0001).Body iron stores (BIS) increased in the intervention group (0.09 mg/kg body weight) and decreased (-0.58 mg/kg body weight) in the reference group at 1 year (p=0.028).These findings indicate an increase in iron deficiency in the reference group and a decrease in the intervention group. However, no changes in serum ferritin and urinary iodine were observed in either group or between groups. CONCLUSIONS: Iron status can be improved in schoolchildren in Tamil Nadu by increasing the amount of micronutrients in the fortified salt used for preparing noon-time school meals.

Comparing the Influence of High Doses of Different Zinc Salts on Oxidative Stress and Energy Depletion in IPEC-J2 Cells.

The current study aimed to investigate the influence of four supplemental zinc salts (chelated: Zn glycine; non-chelated: Zn sulfate, Zn citrate, Zn gluconate) among different zinc concentrations (30-300 µM) on cell proliferation, oxidative stress, and energy depletion in intestinal porcine jejunum epithelial cells (IPEC-J2). Different zinc salts affected cell viability in a time- and dose-dependent manner, which was mainly dependent on the uptake of intracellular Zn2+. Intracellular Zn2+ of Zn sulfate has taken up almost twice as high as Zn glycine when cells were loaded with 100-200 µM zinc. After loading cells with 300 µM zinc, Zn glycine and Zn sulfate had a similar trend in accumulation of Zn2+. When the intracellular Zn2+ overloads, cells will gradually be damaged and subsequently die bearing biochemical features of necrosis or late apoptosis. Meanwhile, obviously, increased levels of intracellular ROS, mitochondrial ROS, MDA, and NO and decreased levels of GSH were observed. Excessive intracellular Zn2+ significantly decreased mitochondria membrane potential accompanied by an obvious loss of ATP and NAD+ levels. Overall, exposure to high doses of zinc salts caused cell damage, which was mainly dependent on the uptake of Zn2+. Zinc overload induced oxidative stress and energy depletion in IPEC-J2 cells, and the cell damage with non-chelated zinc addition was more serious than Zn glycine.

The Possibilities of Using Chromium Salts as an Agent Supporting Treatment of Polycystic Ovary Syndrome.

The polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women in reproductive age with the so far undetermined causes of development. In the etiopathogenesis of PCOS, the role of insulin resistance is emphasised, which was an indication for the attempts at using chromium III salts (Cr) in augmenting pharmacotherapy applied in patients. The analysis of the usefulness and efficacy of this approach was the direct goal of this thesis. Animal tests confirmed the efficacy of chromium in maintaining the appropriate level of glycaemia and insulinaemia, normalisation of plasma concentrations of microelements and also a correlation between the Cr level, insulin and dehydroepiandrosterone (DHEA) was found. A decrease in the expression of 3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase was identified in adipose tissue. Clinical studies, although sparse, show that the supplementation with chromium can improve BMI and the parameters evaluating the control of glycaemia and increase the chances for ovulation and regular menstruation. However, the small number and a variability in study protocols makes comparing them very difficult. A completely new subject that has not been yet studied is the possibility of using chromium in levelling mood disorders in patients with PCOS. Currently, there are still no sufficient proofs for introducing chromium as a standard in treating and preventing insulin resistance in patients with PCOS. However, this direction remains open, and treating insulin resistance is an important challenge in clinical practice.

[Comparison of curative effect and serum electrolytes between different oral rehydration salts in treatment of neurally mediated syncope children].

OBJECTIVE: To compare the curative effect and the changes of serum electrolytes between oral rehydration salts (ORS) I and ORS III treatment in neurally mediated syncope children.
 Methods: The children with the symptom of unexplained syncope and pre-syncope were collected in Second Xiangya Hospital from May 2014 to May 2017. After head-up tilt test (HUTT), their serum electrolytes levels were examined. Children who were positive in the HUTT received ORS (ORS I or ORS III) and health education. Subjects were randomly divided into an ORS I group (n=27) and an ORS III group (n=49).
 Results: There was no statistical significance in sex, age, height, body mass, initial diagnosis and re-diagnosis interval between the 2 groups (P>0.05); the total efficiency after ORS III and ORS I treatment were 79.59% and 62.96%, respectively, with no statistical significance (χ2=2.483, P>0.05); the HUTT negative conversion rate after ORS III and ORS I treatment were 51.02% and 48.16%, respectively, with no statistical significance (χ2=0.058, P>0.05); before treatment, the serum sodium [(140.20±2.26) mmol/L vs (138.39±2.72) mmol/L; t=2.856, P<0.05] in the ORS III group was higher than that in the ORS I group, the serum phosphorus [(1.46±0.19) mmol/L vs (1.65±0.29) mmol/L; t=3.146, P<0.05] in the ORS III group was lower than that in the ORS I group; after treatment, the serum sodium [(140.31±2.01) mmol/L vs (138.88±2.08) mmol/L; t=2.692, P<0.05] and serum calcium [(2.31±0.09) mmol/L vs (2.24±0.11) mmol/L; t=2.696, P<0.05] in the ORS III group were higher than those in the ORS I group, the serum phosphorus [(1.45±0.16) mmol/L vs (1.61±0.25) mmol/L; t=3.128, P<0.05] in the ORS III group was lower than that in the ORS I group; after ORS III treatment, there was no statistical significance in serum electrolytes between HUTT positive group and HUTT negative group (P>0.05); after ORS I treatment, the serum calcium [(2.29±0.10) mmol/L vs (2.19±0.10) mmol/L; t=2.501, P<0.05] and serum phosphorus [(1.71±0.24) mmol/L vs (1.50±0.21) mmol/L; t=2.392, P<0.05] in HUTT positive group were higher than those in HUTT negative group. There was no statistical significance in serum sodium, potassium, magnesium, and chloride (P>0.05); there was no statistical significance in serum electrolytes between pre-treatment and post-treatment in the ORS I group and the ORS III group (P>0.05); there was no statistical significance in serum electrolytes between vasovagal syncope and postural orthostatic tachycardia syndrome in the ORS I group and the ORS III group before ORS treatment (P>0.05). 
 Conclusion: The ORS III and ORS I have the similar efficacy in the treatment of children with neurally mediated syncope. ORS III is easier to be accepted by children than ORS I, with better compliance.

Short communication: Comparison of a palmitic acid-enriched triglyceride supplement and calcium salts of palm fatty acids supplement on production responses of dairy cows.

The objective of our study was to evaluate the effects of feeding a palmitic acid-enriched triglyceride supplement or a calcium salts of palm fatty acid (FA) supplement on nutrient digestibility and production responses of mid-lactation dairy cows. Fifteen Holstein cows (139 ± 39 d in milk) were randomly assigned to treatment sequence in a 3 × 3 Latin square design. Treatments were a control diet (CON; no fat supplement) and 1.5% of FA added either as a palmitic acid-enriched triglyceride supplement (PA-TG) or as calcium salts of palm FA supplement (Ca-FA). Fat-supplemented treatments did not affect dry matter intake (DMI) compared with CON, but Ca-FA reduced DMI compared with PA-TG. Compared with CON, fat-supplemented treatments increased 18-carbon FA digestibility by 2.0 percentage units but did not affect digestibility of total FA or 16-carbon FA. Compared with Ca-FA, PA-TG reduced total FA digestibility by 8.7 percentage units due to a decrease in 16-carbon FA digestibility (21.7 percentage units). Both fat supplements increased neutral detergent fiber (NDF) digestibility compared with CON (3.90 percentage units), and PA-TG tended to increase NDF digestibility by 1.60 percentage units compared with Ca-FA. Compared with CON, fat-supplemented treatments increased milk yield (1.05 kg/d), 3.5% fat-corrected milk yield (2.20 kg/d), and energy-corrected milk yield (1.80 kg/d). Also, PA-TG increased milk fat yield (50 g/d) and milk energy output (1.0 Mcal/d) and tended to increase milk fat content (0.07 percentage units) and energy-corrected milk yield (1.0 kg/d) compared with Ca-FA. Fat-supplemented treatments reduced the yield of de novo milk FA (23 g/d) and increased the yields of mixed (43 g/d) and preformed (52 g/d) milk FA compared with CON. The PA-TG treatment increased the yield of 16-carbon (66 g/d) milk FA compared with Ca-FA, whereas Ca-FA increased the yield of preformed (60 g/d) milk FA. Fat-supplemented treatments increased intake of net energy for lactation by 1.80 Mcal/d, milk energy output by 1.30 Mcal/d, and energy in body reserves by 0.30 Mcal/d compared with CON. The Ca-FA treatment increased energy allocated to body reserves (0.60 Mcal/d), energy partitioning toward body reserves (1.20 percentage units), and body condition score change (0.06 units), and tended to increase body weight change (0.16 kg/d) and body condition score (0.08 units) compared with PA-TG. In conclusion, feeding a palmitic acid-enriched triglyceride supplement increased milk energy output due to increased yields of milk and milk fat, whereas feeding a calcium salts of palm FA supplement increased FA digestibility and energy partitioned to body reserves.

Effects of dietary acidifiers on growth, hematology, immune response and disease resistance of Nile tilapia, Oreochromis niloticus.

Organic acids or their salts can be used as feed additives in aquaculture. This study was conducted to evaluate the use of a mixture of formic acid, propionic acid and calcium propionate compared with oxytetracycline (OTC). A total of 720 apparently healthy Oreochromis niloticus fingerlings with an average body weight of 28.8 ± 0.14 g (mean ± SE) were randomly divided into four equal groups (G1, G2, G3and G4). G1 was fed a basal diet with no additive as the control group, while G2 and G3 were fed a formic and propionic acid/salt mixture in 1 and 2 g/kg, respectively. G4 was fed OTC (0.5 g/kg). Each group was subdivided into tow subgroups A and B (30 fish/subgroup) in triplicate. The first subgroup was used to evaluate growth performance, hematology and body composition for 60 d. The second subgroup was used to examine immunity, gut microbiota and resistance to infection for 30 d. At the end of the feeding period (60 d), G3 had significant improvements in final body weight (FBW), weight gain (WG), specific growth rate (SGR) and food conversion ratio (FCR) compared with other groups. The total erythrocyte count, hemoglobin content, platelet count, hematocrit, mean corpuscular hemoglobin and total leukocyte count were significantly increased in G3 and G2 compared with G1 and G4. Mean corpuscular volum, lymphocyte and neutrophil percentages had the highest significant improvement in G3. There were no significant differences among the groups in mean corpuscular hemoglobin concentration and monocyte percentage. The protein and fat contents of the whole body were the highest in G3. The widest inhibition zones against Aeromonas sobria were at the 30, 40 and 50% concentrations of acidifiers, which were equivalent to OTC (30 µg). G3 showed the lowest total gastrointestinal bacterial counts, followed by G2. After 15 and 30 d, G3 had the highest serum killing, lysozyme and nitric oxide activities. Serum lysozyme activity and nitric oxide assay had no significant difference between G1 and G2 after 30 d. The lowest immune parameters were recorded in G4. After 30 d, the highest expression of interleukin-1ß and tumor necrosis factor-alpha in the liver and kidney were found in G3. The best protection against challenged Aeromonas sobria was in G3, followed by G2 and G4. Dietary supplementation with a combination of formic acid, propionic acid and calcium propionate improves the performance of Nile tilapia.

[The multifunctional therapy of various forms of irritable bowel syndrome]. / Mnogofunktsional'naya terapiya pri razlichnykh formakh sindroma razdrazhennogo kishechnika.

Irritable bowel syndrome (IBS) is a pathological condition characterized by heterogeneous etiology, pathogenesis, and clinical symptoms. These characteristics dictate the necessity of prescribing multiple medications for the treatment of IBS. Such compulsory polypharmacy inadvertently enhances the risk of adverse reactions to the treatment, increases its cost, and impairs compliance on the part of the patients. The objective of the present study was to evaluate the effectiveness of the administration of the clorine-bromine brine with the use of sinusoidal modulated current electrophoresis (SMC-phoresis) for the treatment of different forms of IBS. THE PATIENTS AND METHODS: We examined and treated 80 patients with different forms of IBS. The patients were divided into two equal groups comprised of 40 patients each. The patients of the study group were treated with the use of SMС-phoresis of the bromine-chlorine brine based at the «Varzi-yatchi¼ spa and health resort (the Udmurt Republic) making use of the sparing or stimulating techniques depending on the type of IBS. Each therapeutic course consisted of 10-12 sessions. The patients in the group of comparison received the standard pharmaceutical treatment for IBS (myotropic anti-spasmodics and lactulose). The emphasis was laid on the evaluation of dynamics of the intestinal motor function in different variants of IBS with the use of the EGS-4M apparatus based on the GSRS questionnaire (Gastrointestinal Symptom Rating Scale). Special attention was given to the interpretation of the main gastrointestinal syndromes and the evaluation of the quality of life of the patients in the course of the treatment and after its completion. RESULTS: Тhe main symptoms of IBS after a course of SMC-phoresis with the natural brine were significantly less pronounced compared to those in the patients managed by means of standard pharmacotherapy. Positive dynamics in the clinical picture of the disease had beneficial influence on the quality of life of the patients which approached that of the healthy subjects in the group of comparison. The results of colonography suggested the presence of various types of disturbances of motor function of the intestines. SMC-phoresis of the natural chlorine-bromine brine had a positive influence on dyskinesia associated with diarrhea and constipation associated with IBS, while the effect of the standard pharmaceutical treatment was unidirectional and significantly inferior to it in terms of efficiency. CONCLUSION: The use of complementary therapy can provide a better clinical outcome of IBS and to a greater extent improve the quality of life of the patients presenting with various forms of this pathology.

Effects of salt intake and potassium supplementation on renalase expression in the kidneys of Dahl salt-sensitive rats.

Renalase is currently the only known amine oxidase in the blood that can metabolize catecholamines and regulate sympathetic activity. High salt intake is associated with high blood pressure (BP), possibly through the modulation of renalase expression and secretion, whereas potassium can reverse the high salt-mediated increase in blood pressure. However, whether potassium could also modulate BP through renalase is unclear. In this study, we aim to investigate how salt intake and potassium supplementation affect the level of renalase in rats. Eighteen salt-sensitive (SS) and 18 SS-13BN rats were divided into six groups, receiving normal salt (0.3% NaCl), high salt (8% NaCl) and high salt/potassium (8% NaCl and 8% KCl) dietary intervention for four weeks. At the end of experiments, blood and kidneys were collected for analysis. mRNA level of renalase was measured by quantitative real-time PCR and protein level was determined by Western blot. We found that mRNA and protein levels of renalase in the kidneys of SS and SS-13BN rats were significantly decreased (P < 0.05) after high salt intervention, whereas dopamine in plasma was increased (P < 0.05) compared with rats received normal salt, suggesting that salt may induce salt-sensitive hypertension through inhibition of renalase expression. We also found increased mRNA level and protein level of renalase, decreased catecholamine levels in plasma, and decreased BP in SS rats treated with high salt/potassium, compared with that of the high salt SS group. Taken together, the salt-induced increase and potassium-induced decrease in BP could be mediated through renalase. More studies are needed to confirm our findings and understand the underlying mechanisms.

Methyl Jasmonate Induces Enhanced Podophyllotoxin Production in Cell Cultures of Thracian Flax (Linum thracicum ssp. thracicum).

The Linum thracicum ssp. thracicum cell lines developed in this study are a feasible source for the sustainable production of podophyllotoxin, a lignan with an aryltetralin skeleton that is used for the manufacture of the chemotherapeutic drugs etopophos and teniposide. We used mass spectrometry to confirm the presence of the aryltetralin lignan in the thracian flax cell cultures. Next, we explored how changes in the culture medium influenced the podophyllotoxin content. Out of six developed cell lines, four were selected for further experiments and challenged with elicitors. The selected cell lines clustered into two groups: developed in full strength medium (Li) vs developed in half strength medium (HS). While podophyllotoxin production in the Li cell lines was boosted by 80% upon administration of the elicitor methyl jasmonate, the HS lines produced high amounts of the target metabolite triggered by reduced concentration of nutrients and were only slightly influenced by the elicitor.

Effects of single dose mixed amphetamine salts--extended release on processing speed in multiple sclerosis: a double blind placebo controlled study.

RATIONALE: Multiple sclerosis (MS) commonly affects cognitive function, most frequently presenting as impaired processing speed (PS). There are currently no approved treatments for PS in this population, but previous studies suggest amphetamines may be beneficial. OBJECTIVE: The objective of this study is to determine if mixed amphetamine salts, extended release (MAS-XR) has the potential to improve impaired PS in MS patients in a randomized controlled pre- and post-dose testing study. METHODS: Fifty-two MS patients demonstrating PS impairment on either the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition Test (PASAT) were randomized to a single dose of 5 mg MAS-XR (n = 18), 10 mg MAS-XR (n = 20), or placebo (n = 14). Subjects were evaluated a second time, after taking the blinded medication. ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo. Cohen's d was used to calculate effect size. RESULTS: At baseline, the mean SDMT score was 43.3 ± 7.2 and the mean PASAT was 34.8 ± 13.4, with 47 (90.4 %) and 25 (48.1 %) categorized as impaired on the SDMT and PASAT, respectively. The change in SDMT scores from baseline to post-treatment demonstrated significant improvement for the MAS-XR 10-mg dose compared to placebo, increasing by 5.2 ± 4.5 vs. 0.6 ± 4.4 points (p = 0.043), with a medium effect size of 0.47. Change on the PASAT was not significantly different in either treatment group. CONCLUSIONS: This study supports MAS-XR 10 mg as a potential treatment for MS patients with demonstrated PS impairment, warranting a larger longitudinal study.

Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer.

DDX3 belongs to DEAD box RNA helicase family and is involved in the progression of several types of cancer. In this work, we employed a High Throughput Virtual screening approach to identify bioactive compounds against DDX3 from ZINC natural database. Ketorolac salt was selected based on its binding free energy less than or equals to -5 Kcal/mol with reference to existing synthetic DDX3 inhibitors and strong hydrogen bond interactions as similar to crystallized DDX3 protein (2I4I). The anti-cancer activity of Ketorolac salt against DDX3 was tested using oral squamous cell carcinoma (OSCC) cell lines. This compound significantly down regulated the expression of DDX3 in human OSCC line (H357) and the half maximal growth inhibitory concentration (IC50) of Ketorolac salt in H357 cell line is 2.6 µM. Ketorolac salt also inhibited the ATP hydrolysis by directly interacting with DDX3. More importantly, we observed decreased number of neoplastic tongue lesions and reduced lesion severity in Ketorolac salt treated groups in a carcinogen induced tongue tumor mouse model. Taken together, our result demonstrates that Ketorolac salt is a newly discovered bioactive compound against DDX3 and this compound can be used as an ideal drug candidate to treat DDX3 associated oral cancer.

Comparison of enriched palmitic acid and calcium salts of palm fatty acids distillate fat supplements on milk production and metabolic profiles of high-producing dairy cows.

A variable response to fat supplementation has been reported in dairy cows, which may be due to cow production level, environmental conditions, or diet characteristics. In the present experiment, the effect of a high palmitic acid supplement was investigated relative to a conventional Ca salts of palm fatty acids (Ca-FA) supplement in 16 high-producing Holstein cows (46.6±12.4kg of milk/d) arranged in a crossover design with 14-d periods. The experiment was conducted in a non-heat-stress season with 29.5% neutral detergent fiber diets. Treatments were (1) high palmitic acid (PA) supplement fed as free FA [1.9% of dry matter (DM); 84.8% C16:0] and (2) Ca-FA supplement (2.3% of DM; 47.7% C16:0, 35.9% C18:1, and 8.4% C18:2). The PA supplement tended to increase DM intake, and increased the yields of milk and energy-corrected milk. Additionally, PA increased the yields of milk fat, protein, and lactose, whereas milk concentrations of these components were not affected. The yields of milk de novo and 16-C FA were increased by PA compared with Ca-FA (7 and 20%, respectively), whereas the yield of preformed FA was higher in Ca-FA. A reduction in milk fat concentration of de novo and 16-C FA and a marginal elevation in trans-10 C18:1 in Ca-FA is indicative of altered ruminal biohydrogenation and increased risk of milk fat depression. No effect of treatment on plasma insulin was observed. A treatment by time interaction was detected for plasma nonesterified fatty acids (NEFA), which tended to be higher in Ca-FA than in PA before feeding. Overall, the palmitic acid supplement improved production performance in high-producing cows while posing a lower risk for milk fat depression compared with a supplement higher in unsaturated FA.

Double-blind placebo-controlled randomized clinical trial on the efficacy of Aerosal in the treatment of sub-obstructive adenotonsillar hypertrophy and related diseases.

BACKGROUND: Adenotonsillar hypertrophy (ATH) is a frequent cause of upper airways obstructive syndromes associated to middle ear and paranasal sinuses disorders, swallowing and voice disorders, sleep quality disorders, and occasionally facial dysmorphisms. ATH treatment is essentially based on a number of medical-surgical aids including nasal irrigation with topical antibiotics and corticosteroids and/or treatment with systemic corticosteroids, immunoregulators, thermal treatments, adenotonsillectomy, etc. OBJECTIVES: The aim of the present study is to assess the efficacy of Aerosal halotherapy in the treatment of sub-obstructive adenotonsillar disease and correlated conditions compared to placebo treatment. METHODS: A total of 45 patients with sub-obstructive adenotonsillar hypertrophy were randomized to receive either Aerosal halotherapy or placebo for 10 treatment sessions. The main outcome was a reduction greater than or equal to 25% from the baseline of the degree of adenoid and/or tonsillar hypertrophy. RESULTS: In the intention-to-treat analysis, a reduction of the degree of adenoid and/or tonsillar hypertrophy ≥25% from baseline after 10 therapy sessions was found in 44.4% of the patients in the halotherapy arm and in 22.2% of the patients in the placebo arm (P=0.204). Among the secondary outcomes, the reduction of hearing loss after 10 treatment sessions in the halotherapy arm was higher than the placebo arm (P=0.018) as well as the time-dependent analysis showed significantly improved peak pressure in the Aerosal group (P=0.038). No side effects were reported during the trial. In addition, the therapy was well accepted by the young patients who considered it as a time for play rather than a therapy. CONCLUSIONS: Aerosal halotherapy can be considered a viable adjunct, albeit not a replacement, to conventional medical treatment of sub-obstructive adenotonsillar syndrome and related conditions. Further research is however needed to improve ATH treatment.

Alkaline salts to counteract bone resorption and protein wasting induced by high salt intake: results of a randomized controlled trial.

High sodium chloride (NaCl) intake can induce low-grade metabolic acidosis (LGMA) and may thus influence bone and protein metabolism. We hypothesized that oral potassium bicarbonate (KHCO(3)) supplementation may compensate for NaCl-induced, LGMA-associated bone resorption and protein losses. Eight healthy male subjects participated in a randomized trial with a crossover design. Each of two study campaigns consisted of 5 d of dietary and environmental adaptation followed by 10 d of intervention and 1.5 d of recovery. In one study campaign, 90 mmol KHCO(3)/d were supplemented to counteract NaCl-induced LGMA, whereas the other campaign served as a control with only high NaCl intake. When KHCO(3) was ingested during high NaCl intake, postprandial buffer capacity ([HCO(3)(-)]) increased (P = 0.002). Concomitantly, urinary excretion of free potentially bioactive glucocorticoids [urinary free cortisol (UFF) and urinary free cortisone (UFE)] was reduced by 14% [∑(UFF,UFE); P = 0.024]. Urinary excretion of calcium and bone resorption marker N-terminal telopeptide of type I collagen was reduced by 12 and 8%, respectively (calcium, P = 0.047; N-terminal bone collagen telopeptide, P = 0.044). There was a trend of declining net protein catabolism when high NaCl was combined with KHCO(3) (P = 0.052). We conclude that during high salt intake, the KHCO(3)-induced postprandial shift to a more alkaline state reduces metabolic stress. This leads to decreased bone resorption and protein degradation, which in turn might initiate an anticatabolic state for the musculoskeletal system in the long run.

A randomized trial of copper supplementation effects on blood copper enzyme activities and parameters related to cardiovascular health.

Marginal copper deficiency, which may affect cardiovascular disease risk, is proposed to occur in many adults in Western industrialized countries. The present study tested the hypothesis that in a group of USA adults, increased copper intake would alter readings for blood copper enzymes and markers relevant to cardiovascular disease risk. Healthy middle aged adults with moderately high cholesterol, were given either placebo or copper supplementation (2 mg copper/day as copper glycinate) for 8 weeks. Blood samples were taken before and after the 8 weeks. Copper, but not placebo, raised activities for two copper enzymes, erythrocyte superoxide dismutase 1 and plasma ceruloplasmin. In contrast, five cardiovascular health related plasma parameters were not changed significantly by copper: C-reactive protein, homocysteine, and cholesterol (total, LDL and HDL). However, changes in erythrocyte superoxide dismutase 1 correlated positively with changes in plasma HDL and negatively with plasma homocysteine. Also, copper lowered mean oxidized LDL values, a result that was statistically significant, but inconsistent. In this test population, increased copper intake raised copper enzyme activities, but did not consistently improve the cardiovascular health measures studied.

Drug delivery strategies for poorly water-soluble drugs: the industrial perspective.

INTRODUCTION: For poorly soluble compounds, a good bioavailability is typically needed to assess the therapeutic index and the suitability of the compound for technical development. In industry, the selection of the delivery technology is not only driven by technical targets, but also by constraints, such as production costs, time required for development and the intellectual property situation. AREAS COVERED: This review covers current developments in parenteral and oral delivery technologies and products for poorly water-soluble compounds, such as nano-suspensions, solid dispersions and liposomes. In addition, the use of biorelevant dissolution media to assess dissolution and solubility properties is described. Suggestions are also included to systematically address development hurdles typical of poorly water-soluble compounds intended for parenteral or oral administration. EXPERT OPINION: A holistic assessment is recommended to select the appropriate delivery technology by taking into account technical as well as intellectual property considerations. Therefore, first and foremost, a comprehensive physico-chemical characterization of poorly water-soluble compounds can provide the key for a successful selection and development outcome. In this context, the identified physical form of the compound in the formulation is used as a guide for a risk-benefit assessment of the selected oral delivery technology. The potential of nano-suspensions for intravenous administration is unclear. In the case of oral administration, nano-suspensions are mainly used to improve the oral absorption characteristics of micronized formulations. The development of an in situ instantaneous solubilization method, based on stable, standardized liposomes with low toxicity, opens new avenues to solubilize poorly water-soluble compounds.

Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: II. Neutrophil fatty acids and function, and acute phase proteins.

The objectives were to evaluate the effects of differential supplementation of Ca salts (CS) of fatty acids (FA) on plasma acute phase proteins and both FA composition and function (i.e., activity and cytokine production) of neutrophils, during the peripartum and breeding periods. Holstein cows were assigned randomly to receive either CS of palm (PO) or safflower (SO) oils from 30 d prepartum until 35 d postpartum (dpp) and CS of PO or fish oil (FO) from 35 to 160 dpp. Supplementation of CS of FA was at 1.5% of dietary dry matter. Cows (n=32) were sampled three times weekly from parturition to 35 dpp for analyses of plasma concentrations of haptoglobin and fibrinogen. Cows (n=47) were sampled for neutrophil phagocytic and oxidative burst activities toward Escherichia coli and Staphylococcus aureus, and neutrophil abundances of L-selectin and ß(2)-integrin assessed by flow cytometry at 32 d prepartum, within 7h after parturition, and 4 and 7 dpp. Profiles of FA in neutrophils and cytokine production (i.e., tumor necrosis factor alpha, TNF-α, and IL-1ß) were assessed prepartum (n=14), 35 (PO vs. SO; n=26) and 85 dpp (PO vs. FO; n=28). Plasma concentrations of haptoglobin and fibrinogen were greater for cows fed SO compared with PO. The percentage of neutrophils with phagocytic and oxidative burst activities was not affected by transition diets, but activities per neutrophil were greater in SO compared with PO diets at 4 (phagocytosis and oxidative burst) and 7 dpp (oxidative burst). Neutrophil abundance of L-selectin, but not ß(2)-integrin, was greater in SO compared with PO at 4 and 7 dpp. Neutrophil productions of TNF-α and IL-1ß were increased at 35 dpp in SO compared with PO diets, but production of TNF-α was attenuated in FO compared with PO at 85 dpp. Neutrophil ratios of n-6:n-3 FA were greater at 35 dpp in the SO diet and less at 85 dpp in FO compared with PO diets. In conclusion, cows supplemented with CS of SO had improved innate immunity (i.e., acute phase response and neutrophil function) to better cope with the bacterial challenges in the postpartum period. Conversely, CS of FO attenuated neutrophil cytokine production.

Milk composition, milk fatty acid profile, digestion, and ruminal fermentation in dairy cows fed whole flaxseed and calcium salts of flaxseed oil.

Four ruminally lactating Holstein cows averaging 602+/-25 kg of body weight and 64+/-6 d in milk at the beginning of the experiment were randomly assigned to a 4 x 4 Latin square design to determine the effects of feeding whole flaxseed and calcium salts of flaxseed oil on dry matter intake, digestibility, ruminal fermentation, milk production and composition, and milk fatty acid profile. The treatments were a control with no flaxseed products (CON) or a diet (on a dry matter basis) of 4.2% whole flaxseed (FLA), 1.9% calcium salts of flaxseed oil (SAL), or 2.3% whole flaxseed and 0.8% calcium salts of flaxseed oil (MIX). The 4 isonitrogenous and isoenergetic diets were fed for ad libitum intake. Experimental periods consisted of 21 d of diet adaptation and 7 d of data collection and sampling. Dry matter intake, digestibility, milk production, and milk concentrations of protein, lactose, urea N, and total solids did not differ among treatments. Ruminal pH was reduced for cows fed the CON diet compared with those fed the SAL diet. Propionate proportion was higher in ruminal fluid of cows fed CON than in that of those fed SAL, and cows fed the SAL and CON diets had ruminal propionate concentrations similar to those of cows fed the FLA and MIX diets. Butyrate concentration was numerically higher for cows fed the SAL diet compared with those fed the FLA diet. Milk fat concentration was lower for cows fed SAL than for those fed CON, and there was no difference between cows fed CON and those fed FLA and MIX. Milk yields of protein, fat, lactose, and total solids were similar among treatments. Concentrations of cis-9 18:1 and of intermediates of ruminal biohydrogenation of fatty acids such as trans-9 18:1 were higher in milk fat of cows fed SAL and MIX than for those fed the CON diet. Concentration of rumenic acid (cis-9, trans-11 18:2) in milk fat was increased by 63% when feeding SAL compared with FLA. Concentration of alpha-linolenic acid was higher in milk fat of cows fed SAL and MIX than in milk of cows fed CON (75 and 61%, respectively), whereas there was no difference between FLA and CON. Flaxseed products (FLA, SAL, and MIX diets) decreased the n-6 to n-3 fatty acid ratio in milk fat. Results confirm that flax products supplying 0.7 to 1.4% supplemental fat in the diet can slightly improve the nutritive value of milk fat for better human health.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53 percent), TIMP-1 (-31.7 percent), TGF-β1 (-57.7 percent), and MMP-2 (-41.6 percent), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1 percent), ALT (-17.6 percent), and AST (-12.2 percent) serum levels; c) increased liver weight (11.3 percent), and reduced liver collagen (-37.1 percent), regenerative nodules size (-22.1 percent), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.