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The aim of this trial was to investigate the effects of a blend of monoglycerides of short- and medium-chain fatty acids (SMCFA) on health status and growth of preweaned male calves from 16 to 72 days of age. The in vivo study was conducted as a complete randomised block design. Twenty Italian Holstein calves received starter administered ad libitum and 6 L of milk replacer/day (12% powder concentration) and were divided into treated (T) and control (C) groups. A preliminary in vitro antibiotic activity test of SMCFA was performed on several bacterial strains showing a minimum inhibiting concentration ranging from 0.8 to 12.5%. The group T received SMCFA (11 g/day) within the milk replacer while, to obtain isoenergetic liquid diets, the group C received additional 18 g/day of milk replacer powder. Body weight and morphological measurements of the calves were performed weekly. Health scores were checked daily. Faecal and blood samples were collected every two weeks for routine clinical investigations including serum concentration of non-esterified fatty acids and β-Hydroxybutyric acid. At the end of the trial calves were slaughtered and gastrointestinal tract (GIT) organs weighed. The group T reported a better health status and did not require Ab therapy. No differences in biometrical measurements, feed efficiency, blood parameters, and GIT measures were found between the two groups. At 44 days of age, group T showed higher β-Hydroxybutyric acid concentration compared to group C (p

Bitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the "taster" PAV and the "non-taster" AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.

This study investigated the fertility of dairy cows during summer season after treatment with a single or double PGF2α in a progesterone (P4)-based Ovsynch protocol for fixed-time artificial insemination (FTAI). The data were compared to a treatment effectuated during winter season. Two groups of 60 dairy cows each were randomly assigned on day 60 post-partum to single PGF2α or double PGF2α group. At removal of the P4 treatment the single PGF2α group received a single dose and the double PGF2α group received two doses of PGF2α at 24 hours apart. In each group, 30 cows were treated during the summer (June, July and August) and 30 cows during the winter (December, January and February) season. During summer season a double PGF2α dose did not influence pregnancy rate at FTAI but improved cumulative pregnancy rate 60 days after FTAI (43% vs 69% for single PGF2α and double PGF2α administration, respectively; P2α administration did not modify PR or cumulative PR. In conclusion, during summer the utilization of a double instead of single PGF2α treatment into a P4-based Ovsynch-FTAI protocol did not increase pregnancy rate at FTAI but improved cumulative pregnancy rate.

This manuscript introduces BITTSy, the Behavioral InfantToddler Testing System. This software system is capable of running the headturn preference procedure, preferential looking, conditioned headturn, and visual fixation/habituation procedures. It uses only commercial-off-theshelf (COTS) hardware to implement the procedures in an affordable and space-efficient setup. The software package, example protocols and data sets, and manual are freely available and downloadable from go.umd.edu/BITTSy, making this entire set of procedures available to resource-limited labs. Researchers can easily use BITTSy at multiple sites in a uniform manner, resulting in a standardized, powerful research tool that can enhance cross-site research collaborations.

Simple Summary While cows are usually monovular, the incidence of dizygous twin births has recently increased considerably alongside increasing milk production. Genetic progress and improvements in nutrition and management practices have led to a continuous increase in milk yield and thus also to multiple ovulations and twin pregnancies. Twin pregnancies are undesirable as they seriously compromise the welfare of the cow and herd economy. A better understanding of the processes associated with multiple ovulations should help to reduce rates of twinning. During the stages of the sexual cycle, temperature gradients are established within the ovary and throughout the genital tract. Pre-ovulatory local cooling of the reproductive system favors male and female gamete maturation and subsequent fertilization. In fact, thermal mechanisms may prevent or favor multiple ovulations and thus twinning. The purpose of this review was to update this topic. Abstract While cows are predominantly monovular, over the past 30 years the incidence of multiple ovulations and thus twinning has increased considerably alongside milk production. Multiple pregnancies are not desirable as they negatively affect the health of cows and the herd economy. Although causal mechanisms associated with multiple ovulations have been extensively revised, the process of multiple ovulations is not well understood. Recent studies on the thermal biology of the reproductive system have shown how thermal mechanisms may prevent or favor multiple ovulations. This review focuses on this relationship between thermal dynamics and multiple pregnancies. Cooling of the pre-ovulatory follicle is able to regulate ovulation. In effect, pre-ovulatory local cooling of the female reproductive system favors male and female gamete maturation and promotes fertilization. Thermal stress is proposed here as a model of stress. Periods of high ambient temperature affect the processes of pre-ovulatory follicular cooling and multiple ovulations. While the ratio between unilateral and bilateral multiple pregnancies is normally close to one, under heat stress conditions, this ratio may be 1.4 favoring unilateral multiple pregnancies. A ratio approaching unity is here proposed as an indicator of cow wellbeing.

In the Northern Hemisphere, from June to September and in the Southern Hemisphere from December to March, there are periods of reduced fertility (sub-fertility) in dairy cows that are described as summer infertility. Several factors contribute to sub-fertility during this time, such as ambient temperature, humidity and photoperiod. During the warm season there is a reduction in feed intake that may compromise the energy balance of the cow and/or induce an imbalance in the activity of the hypothalamo-hypophyseal-ovarian axis. These factors reduce the reproductive performance of the cow and compromise the quality of oocytes, embryos and corpora lutea. This paper reviews current knowledge on the metabolic and endocrine mechanisms that induce summer infertility and describe their effects on follicle, oocyte and embryo development in dairy cows.

The seasonality of reproduction in most mammals is dictated by photoperiod, temperature and nutrition. Melatonin, mainly synthesized in the pineal gland, is generally accepted as the active mediator of photoperiod responses including reproduction. While non-pregnant heifers and cows show continuous sexual activity and are therefore not seasonal breeders, it has been suggested that photo-periodicity may influence the appearance of puberty in heifers and the onset of parturition. Further, the light/dark ratio may influence endocrine patterns of gestation and a shorter light period correlates with the incidence of twin pregnancies. This review considers specific aspects of the effects of photoperiod and melatonin on reproduction in dairy cattle and discusses the clinical applications of melatonin.

The physical and gynecological examination of a Holstein heifer single-born with a disorder of sexual development showed anatomical abnormalities such as the presence of a scrotum and 2 vulvae and an anal sphincter that was positioned on the right side of the body. Also, an early pregnancy was diagnosed. Cytogenetic and hormone analysis was requested, and the animal showed normal female metaphases (60,XX) and hormonal profiles. However, in gross anatomy and histological examinations, a structure compatible with a penis, the absence of a uterine body, 2 exophytic structures, and a septum in the vagina were detected.

Adducts of TiCl

In the present study the Authors developed a new modified boar semen extender for short-term liquid storage, based on the use of amikacin sulphate and fructose rather than gentamicin and glucose. The new extender (ME-S) was evaluated and compared in vitro to commercial ones (CRONOS ™ , TRIXcell ™ ) and to a modified extender designated for long term storage (ME-L) for progressive motility. Progressive motility was not different (P40.05) among extenders until 120 h of storage, as differences among extenders became significant (Po0.05) at 144 and 166 h. Motility data across time were better for ME-S than

Prostate cancer is one of the most important malignancies in men. In old men the frequency of prostate cancer at necroscopy has been reported to exceed 40%. Dogs are the only large mammals other than humans with a significant incidence of spontaneous prostate cancer. Adenocarcinoma, transitional cell carcinoma and undifferentiated carcinoma are the most common histological type but the precise cell of origin in dog is not known. The incidence of prostatic carcinoma in dogs is low (0.2% - 0.6%). Prostatic carcinomas occur in sexually intact and neutered dogs and the risk increase in castrated dogs associated to pulmonary and bone metastases. The castration does not initiate the development of prostatic carcinoma in dog but does favour tumour progression. In men the early stage detection of prostate cancer can offer various therapies as radical prostatectomy, radial therapy, thermal ablation, anti-androgen therapy, chemotherapy. In dogs the diagnosis is often in advanced stage of the cancer and the survival time for dogs with prostate cancer is poor. The median time reported is 30 days after diagnosis. In this study we reported three cases of prostatic carcinoma in intact sexually dogs and one in a neutered dog. The sexually intact subjects were older (mean age = 10.5 years) and they had prostatic adenocarcinoma (PCA). The interval between castration and onset of prostatic problems was 3 years. All the dogs showed dysuria, macroscopic hematuria, dyschezia and ataxia. All dogs have been euthanized in order to relieve pain and suffering.

Standardbred maiden mares are generally stressed and in poor physical condition because of their incorrect management at the end of their racing careers. The purpose of this study was to identify an objective assessment that, similar to body condition score (BCS) determination, is easy to measure and able to confirm or improve fattening status assessment, as well as to ascertain whether a relationship with reproduction efficiency exists in subjects destined for a first-time insemination program. The authors assessed 29 Standardbred maiden mares (7 ± 2 years old) during the breeding season. On January 15 (day 0), the same operator performed the following on all subjects: the first gynecological and ultrasound examination, a BCS assessment (range 0 to 5), and an adiposity objective assessment (i.e., measurement of fat thickness by ultrasound scan). At day 0, all mares were in seasonal anestrous. On ovulation day, all subjects exited the study. Both techniques were shown to be significantly and reciprocally correlated (r = 0.976; P

The aims of the study were to identify microbial flora in boar semen under field conditions in northern Italy, to investigate antibiotic resistance and sensitivity of isolated bacteria, and to evaluate elimination of bacteria after storage in two types of extenders added with different antibiotics (amikacin vs gentamicin). A total of 60 boars were collected in 13 pig farms. Bacteriological and mycological investigations were performed immediately on raw semen samples, then at 48 and 120 h of storage on semen diluted randomly in a new short-term modified extender (ME-S) or in a commercial one (CRONOSTM). Bacterial contamination was found in 63% of raw semen samples and different bacterial species were isolated: E.coli, Serratia marcescens, Staphylococcus epidermidis and aureus, Proteus spp., Streptococcus spp. and Pseudomonas aeruginosa. E. coli was the most isolated contaminant (53%); Pseudomonas aeruginosa was found only in one semen sample. The analysis of variance of factors affecting contamination levels was significant for the farm of origin (P

Several polypropene samples, synthesized with different catalytic systems based on TiCl4 supported on activated MgCl2 and different electron donors, were studied using both preparative and analytical temperature-rising elution fractionation (TREF). The experimental results show that each variation in the catalytic system is clearly reflected in the nature of the corresponding polymer, which can be distinguished by both preparative temperature rising elution fractionation and analytical temperature rising elution fractionation dissolution profiles.

In the first days after birth is common to see weight loss in puppies that should not exceed 10% of body weight at birth. The main causes of weight loss are urine and meconium issued followed by non-recovery of fluids expelled. The aims of the study were to check and outline growth curves in boxer breed during the first two week of life. In our study between 3th and 5th day after birth puppies retrieved the weight and got back a gain that leads to double in two weeks. We observed a mean weight loss of 11.26 g (2.27%) between the first two days of life, subsequently they recovered the birth weight on day four. In our study puppies that regained the birth weight earlier were the puppies with higher weight at birth and were the heaviest at day 13.

The copolymerization of propylene with small amount of ethylene using MgCl2-supported stereospecific catalysts in combination with different Al-alkyls was performed. At least for the particular catalyst used, it resulted that TEA and TIBA are the preferred Al-alkyls; whereas, the mixture TEA/DEAC provides copolymers with a high amount of xylene solubles. Finally, the mixture TEA/DEAI largely decreases catalyst activity, but it provides a copolymer with broad MMD.

Growth hormone (GH) hypersecretion is associated with an increased incidence of cardiac hypertrophy and subclinical abnormalities of left ventricular (LV) function. The unlimited availability of biosynthetic GH has led to progressively increased dosage when treating GH-deficient children, raising the question of its cardiovascular effects during long-term therapy. We compared 22 children (8 girls, 14 boys), mean age 12.1 years (range 3–17 years) with GH deficiency who were receiving chronic GH treatment (GH group) with 22 normal controls matched for sex and body size in order to evaluate: (1) LV volume, mass, and systolic function by two-dimensional guided M-mode echocardiography; (2) LV diastolic function by pulsed-wave Doppler sampling of the transmitral flow; and (3) cardiac output and systemic vascular resistance by Doppler echocardiography. All patients had been on chronic GH therapy for 13.8±7.6 months (range 5–30 months) with an average dose of 0.95±0.12 IU/kg per week (range 0.69–1.17 IU/kg per week). Blood pressure did not differ between the two groups. LV volume, mass, ejection fraction, and mean velocity of circumferential shortening did not differ significantly between the GH group and controls; nor did the peak- and end-systolic meridional stress. All patients had a normal contractile state as estimated by the relation between mean velocity of circumferential shortening and end-systolic meridional stress. The LV filling parameters did not differ between the two groups, and there was no difference in cardiac index and systemic vascular resistance. These f9ndings suggest that long-term treatment with high doses of GH in GH-deficient children and adolescents does not lead to adverse cardiac effects. Whether longer-duration therapy could cause morphofunctional alterations of the left ventricle requires further investigation.

XPS, SEM, SSIMS, FTIR-ATR, water-in-air, and air-in-water contact angle measurements have been used to unambiguously characterize the locus of failure of PP/epoxy joints. In the case of untreated PP, the fracture has been found adhesive, whereas in oxygen plasmatreated PP, it is cohesive, within bulk PP, but close to the modified PP-bulk PP interface. The smoothness of fracture surfaces allowed us to exclude mechanical interlocking effects. Shear-strength measurements showed that the mechanical strength of the joint was improved by plasma treatment. Preliminary thermal equilibration of the plasma-treated PP sample and changes in the curing cycle of the epoxy resin did not change either the locus of failure or the shear strength of the joint. The reason is probably because the number of polar functions left at the surface after thermal equilibration is sufficient to induce adhesion. The mechanical strength of the PP surface layer may be the determining factor. Fracture energy calculations showed that the observed locus of failure is the same as predicted on the basis of surface energy considerations.

Oxygen plasma treatment of polypropylene (PP) surfaces led to introduction of oxygencontaining functionalities, with consequent improvement of surface wettability. A combination of X-ray photoelectron spectroscopy (XPS), static secondary ion mass spectroscopy (SSIMS), and contact angle measurements (water-in-air and air-in-water) allowed us to characterize the behavior of the treated surface in contact with air (low-energy surface) and water (high-energy surface). The treated surface showed the tendency to rearrange itself to minimize its interfacial energy. When contacted with air (low-energy surface), polar groups were buried away from the polymer/air interface, while in contact with water (high-energy surface) polar groups remained at the polymer/water interface. When contacted with air, the polymer surface layer rearranged by macromolecular motions within itself, since interdiffusion with the bulk polymer seems forbidden. These motions are thermally activated and it was possible to obtain an apparent activation energy (58.1 kJ/mol) close to those reported for other vinyl polymers.

In its hospitals, the local Reggio Emilia Division of the National Health Service has introduced beds and stretchers with up-and-down movement systems, electrical lifters for patients, and highly mobile trained more than one thousand workers in the correct execution of maneuvers for moving patients manually platforms and litters for transferring patients from stretcher to bed. The Division has also. The risk evaluation models available in the literature have proved to be inadequate for instituting a program of improving service or for adequately supporting the doctor in charge. To overcome these limitations, a standard of risk evaluation called SpoSo ("Spostamenti Sollevamenti"--"Moving and Lifting") has been experimentally adopted.

The role of central and peripheral histamine H3 receptors in the regulation of gastric acid secretion and gastric mucosal integrity is reviewed. The activation of H3 receptors by peripheral administration of the selective agonist (R)alpha-methylhistamine reduced acid secretion in cats, dogs, rats and rabbits, while increasing it in mice. The antisecretory effects were observed against indirect stimuli that act on vagal pathways or on enterochromaffin-like (ECL) cells, such as 2-deoxy-D-glucose, food or pentagastrin, but not against histamine or dimaprit. Inhibitory effects on acid production were observed in rats after central administration of histamine or of H3 receptor agonists. In the conscious rat intragastric administration of (R)alpha-methylhistamine caused gastroprotective effects against the damage induced by absolute ethanol, HCl, aspirin and stress. The mechanism involved seems to be related to the increased mucus production, via nitric oxide-independent mechanisms. Gastroprotective effects against ethanol were also observed after central administration of histamine or its metabolite N(alpha)-methylhistamine, suggesting that brain receptors participate the histamine-mediated effects on gastric functions.

The assessment of the protective actions of H2-receptor antagonists against gastric mucosal lesions by necrotizing agents relies on the gross observation of the gastric mucosa only. We examined the activity of famotidine against 0.6 N HCl-induced damage and the role of parietal cells by light and transmission electron microscopy. Rats received famotidine 0.3-10 mg/kg intragastrically. Sixty minutes later 0.6 N HCl (1 ml/rat) was given and after an additional 30 min the stomachs were removed. Macroscopically visible lesions were measured. Histologic lesions were scored on the basis of the depth. The ultrastructure of parietal cells in the isthmus-neck region was examined. Pretreatment with famotidine resulted in a slight increase of macroscopically visible gastric lesions in response to HCl. While the extent of total histologic damage was not modified, the antisecretory dose significantly reduced only lesions deep within the mucosa. Famotidine alone determined the dose-dependent occurrence of a distinct parietal cell morphological state, suggestive of inhibition of the secretory system. A causal link between the protective effect on the region where parietal cells are located, the percentage of cells shifting to the inhibited morphological state, and the inhibitory effect on acid secretion is proposed.

The histamine H(3) receptor shows high degree of stereoselectivity for histamine analogues branched in the side chain. The hypothesis that gastroprotection by (R)-alpha-methylhistamine could be H(3) receptor-mediated was tested by comparing the effect of (R)-alpha-methylhistamine and of (S)-alpha-methylhistamine on ethanol-induced histologic lesions in the rat gastric mucosa. Extensive damage was caused by 60 min exposure to absolute ethanol, 91% of the mucosa examined being damaged. Conversely only 23% of the mucosa was damaged after pretreatment with (R)-alpha-methylhistamine (100 mg/kg i.g.). In the groups pretreated with (S)-alpha-methylhistamine (55.44 and 166.3 mg/kg i.g.) total damage ranged from 77 to 79%, though it was confined to the upper portion of the mucosa. Morphometric analysis of stained intraepithelial mucosubstances revealed that (R)-alpha-methylhistamine pretreatment resulted in an increase in number and volume of surface mucous cells, not evident after (S)-alpha-methylhistamine pretreatment. Scanning electron microscopy confirmed light microscopy evaluations. The two isomers of alpha-methylhistamine differently affect the response of rat gastric mucosa to absolute ethanol and they appear to differ in their influence on surface mucous cells. A basis for interpreting the effects of the two isomers of alpha-methylhistamine rests on the high degree of stereoselectivity of H(3) receptors and on the different affinities of the two isomers for these receptors.

The effect of the nonsteroidal antiinflammatory drug (NSAID) amtolmetin guacyl (AMG) on the gastric mucosa was studied in the rat by means of histological and functional techniques. AMG administered at 50-300 mg/kg intragastrically was virtually devoid of gastrolesive properties after either acute or repeated treatment. By contrast, its metabolite, tolmetin (TOL, 15-60 mg/kg, intragastrically) caused dose-dependent gastric damage after both treatments. Light and electron microscopy revealed that AMG induced minimal changes in the surface epithelium layer, without signs of vasocongestion or leukocytes adherence. AMG (50 mg/kg intragastrically) did not change basal gastric potential difference (PD), whereas acetylsalicylic acid and ibuprofen induced falls in PD of 22 and 27 mV, respectively. AMG (50 mg/kg intragastrically) reduced by 60% the fall in PD induced by 50% ethanol; this inhibition was dependent on the incubation time, and was maximal when AMG was given 4 hr before ethanol. AMG (100 mg/kg intragastrically) induced an increase in NO synthase type 2 (NOS2) activity, which was significantly different from control values, when AMG was administered 4 hr before the test. The metabolites of AMG, tolmetin, MED 5, and guaiacol were ineffective. Pharmacokinetic analysis of the residence time of AMG in the different areas of the gastrointestinal tract, revealed that AMG remains in the gastrointestinal tract at least for 4 hr, the time necessary for a maximal induction of NOS2 and for maximal protection against ethanol-induced damage. In conclusion, these data indicate that the nonsteroidal antiinflammatory drug amtolmetin guacyl is devoid of gastrolesive properties; this gastro-sparing effect seems to involve the production of nitric oxide, which can counteract the damaging effects due to prostaglandin inhibition. The presence in the stomach of the native molecule of amtolmetin guacyl seems to be necessary for the protective effect observed.

Hoffa's fat pad disease is characterized by chronic knee pain mostly under the patella. Acute cases are generally post-traumatic; the clinical picture consists of especially anterior pain and functional impairment mimicking a ligament injury, often in the presence of a bulky effusion even with blood from mucous ligament arteriole rupture. In chronic cases, recurrent episodes of hydrarthrosis are reported, together with joint weakening and subpatellar discomfort. At clinical examination, Hoffa's sign is difficult to observe but can be highly specific. Extending a bent knee putting pressure on the patellar tendon margins elicits a strong pain, an antalgic block and a defensive behavior of the patient. MRI clearly depicts Hoffa's infrapatellar fat pad and its findings may suggest the frequently ignored diagnosis of Hoffa's syndrome, alone or associated with other local or systemic conditions. This is really important for a complete and correct surgical planning, since the classic anterolateral arthroscopy and arthrotomy never visualize the pad itself and, at any rate, give no information on the possible changes.June 30, 1995, to June 30, 1997, one hundred and ninety-three arthroscopies were performed at the Service of Orthopedics of Argenta Hospital. The present retrospective study excluded 107 patients (65.45%) who had not undergone MRI. In the remaining 86 patients (44.55%) who underwent MRI, the surgical, arthroscopic and nonarthroscopic patterns of Hoffa's pad were studied and 17 patients selected for surgical curettage of Hoffa's pad which was the site of isolated or associated conditions. All 17 MR examinations were reviewed to assess the patterns of the various pad abnormalities in the light of the surgical picture and of the latest indications from the international literature.T1-weighted sequences showed the fibrotic trabeculae of the pad thanks to the contrast offered by hyperintense fat and T2-weighted sequences demonstrated liquid infiltration in the pad and various synovial recesses. Despite the limitations of a retrospective study, MRI had high sensitivity in Hoffa's fat pad studies in our 17 patients; its specificity depended on the condition. MRI was particularly reliable in acute (Hoffa's pad rupture-detachment) and chronic conditions with aspecific hypertrophy (chondromatosis, pigmented villonodular synovitis), as well as in systemic disorders (rheumatoid arthritis).Accurate studies of Hoffa's fat pad are mandatory because different pad injuries may require a different arthroscopic approach from the classic ones. MRI was a useful tool in the study of Hoffa's fat pad, whose local and systematic involvement is an often ignored cause of anterior knee pain.

Insulin resistance (IR) in dogs is suspected when hyperglycemia is present despite administration of insulin doses greater than 1.0 to 1.5 UI/kg. IR is caused by increases in counter regulatory hormones concentrations (glucagon, glucocorticoids, catecholamines and growth hormone). This study was conducted to investigate the use of aglepristone (RU 46534), a P4 receptor antagonist, for the treatment of IR diabetes mellitus in bitches during the luteal phase. All animals were treated with porcine insulin zinc suspension (Caninsulin) and aglepristone (Alizin) 10 mg/kg subcutaneously at day 1, 2, 9 and 17 from diagnosis. At day 5, no significant variation in glycemia was shown. At day 12 and 20, serum glucose concentrations were significant lower (p < 0.05). From day 12 the insulin dose was reduced to 0.8 IU BID. Insulin was reduced in the following weeks and glycemia was controlled.

The effect of a new histamine H2-receptor antagonist derived from the lamtidine molecule and containing a nitric oxide (NO)-donor furoxan moiety (derivative 1) was studied for its gastric antisecretory activity and for a possible gastroprotective effect, in comparison with the analog without the furoxan moiety (derivative 2). The H2-receptor antagonistic activity was also investigated in the isolated guinea pig papillary muscle. Derivative 1 was approximately 10 times less potent than derivative 2 at the H2-receptor level; conversely, it was about 10 times more effective as a gastroprotective agent against ethanol- and 0.6 N HCl-induced gastric lesions. The mechanism of the gastroprotection exerted by derivative 1 is probably connected with the release of NO, whose vasodilating action on gastric mucosa vessels is crucial. The combined antisecretory and gastroprotective activity of derivative 1 allows this compound to be considered as a prototype of a new class of antiulcer agents.

(R)-alpha-Methylhistamine, a selective agonist of histamine H3 receptors, prevents macroscopically visible gastric lesions by absolute ethanol in the rat. A further insight into its activity was the aim of our study. Rats were given saline or (R)-alpha-methylhistamine (100 mg/kg) intragastrically. After 30 min, absolute ethanol was given and gastric mucosa was sampled 60 min later. Histologic damage and intracellular and adherent mucus were quantified. Luminal surface and mucous cells were examined by scanning and transmission electron microscopy. (R)-alpha-Methylhistamine reduced the extent of lesions by ethanol from 96 to 18%. Surface mucous cells and mucous neck cells were increased in volume and number, packaging of intracellular mucus was modified, and the secretory processes were promoted by (R)-alpha-methylhistamine itself, although these modifications were mostly evident in stomachs subsequently exposed to ethanol. Adherent mucus layer thickness was increased by (R)-alpha-methylhistamine only after ethanol exposure. It is concluded that (R)-alpha-methylhistamine predisposes mucous cells to react to ethanol.

The ability of (R)-alpha-methylhistamine, the selective agonist of histamine H3 receptors, to reduce ethanol-induced gastric damage was examined in the rat. (R)-alpha-methylhistamine (1-100 mg/kg intragastrically) caused a dose-related reduction in the amount of damage produced by ethanol. This protective effect was not shared by the S enantiomer of alpha-methylhistamine. Thioperamide, selective H3 receptor antagonist, inhibited the protective effect of 10 but not 100 mg/kg of (R)-alpha-methylhistamine. Pretreatment with (R)-alpha-methylhistamine, 100 mg/kg i.g., resulted in a significant increase in the thickness of adherent mucus gel layer, which may contribute to the protective action of the compound.

This work was aimed at investigating US reliability in the diagnosis of rotator cuff lesions. A series of 554 patients with a chronically painful shoulder submitted to US was retrospectively reviewed to search for any possible rotator cuff lesion. US demonstrated total or partial cuff tears in 82 potentially surgical patients (14.8%) Then, in this group, the occurrence of every US sign was investigated. Cuff disappearance was observed in 42 patients (51.2%), convexity loss in 20 (24.4%), cuff thinning in 17 (20.75%) and focal discontinuity in 3 patients only (3.7%). In the second part of the study, we considered only 33 surgical patients. Surgery confirmed cuff tears in 30 patients (90.9%), whereas in 3 false-positive patients US had overestimated focal hyperechoic areas and tendon thinning. Thus, our study confirms the almost absolute sensitivity of some US signs of cuff lesions, e.g., cuff disappearance and convexity loss, in the screening of the patients with a chronically painful shoulder. On the contrary, when focal hyperechoic lesions or tendon thinning are present and US poorly demonstrates them, potentially surgical patients must be submitted to MRI.

This study examined the gastroprotective effect of (R)-alpha-methylhistamine (MHA), a selective agonist of histamine H3 receptors. Gastric lesions were induced in the rat by administering absolute ethanol in a volume of 1 ml. Stomachs were removed 1 h later and lesions evaluated both macroscopically and histologically. MHA dose-dependently inhibited ethanol-induced lesions in the range 1-100 mg/kg both by the intragastric and intraperitoneal route. Histological findings indicated that the number of mucous granules in surface and neck cells was increased and the process of reepithelialization was rapidly promoted by MHA. Thioperamide, at 10 mg/kg, inhibited the protective effect of 10 but not of 100 mg/kg of MHA. Larger doses of thioperamide could not be tested because of an interaction with ethanol causing central nervous system effects. Famotidine and indomethacin pretreatment only partially counteracted the MHA effect. The results indicate that MHA is highly effective in preventing ethanol-induced lesions but the exact mechanism is still uncertain.

Fifteen intra-articular fractures of the knee were treated by reduction under arthroscopic monitoring and osteosynthesis, and followed-up after an average of 24 months. The authors expose the principles of surgery and discuss the advantages and the disadvantages as compared to traditional surgery.

Ultrasonography is the method of choice in the study of rotator cuff tears, a very frequent event especially as the final outcome of the impingement syndrome. The authors investigated US sensitivity with the retrospective review of 20 surgical patients with a chronically painful shoulder. US sensitivity was 85%, with 15% false-negative results. Seventeen true-positive cases were restudied for the three main US signs of cuff tear: marked tendon thinning was observed in 64.7% of cases, cuff disappearance in 23.5% and focal discontinuity in 11.8%. This retrospective study confirms that, whenever US shows a cuff tear, the diagnosis can be made, while when US findings are negative or questionable, but clinics are positive, MRI must be performed.

Starting from the structure of thioperamide, a known H3-antagonist, a new series of compounds with a benzothiazole nucleus instead of the cyclohexylcarbothioamide moiety was synthesized. Various substituents, selected by experimental design, were introduced in position 6 of the benzothiazole nucleus, in order to change its physico-chemical characteristics. The lipophilicity of the synthesized compounds was measured by means of RP-HPLC, and their H3-receptor affinity was evaluated by competitive binding assays on rat cortex synaptosomes, with the labelled ligand N alpha-[3H]methylhistamine. A QSAR analysis was performed on the experimental data, using also substituent constants taken from the literature. The newly synthesized compounds showed lower H3-affinities than thioperamide; quantitative structure-activity relationships, described by models obtained with PLS and MRA techniques, were observed among benzothiazole derivatives. According to these relationships, any attempt to improve the potency of these compounds should involve the substitution of the benzothiazole moiety with less bulky and/or more flexible structures, which should also be less lipophilic and allow better electronic interactions with the binding site. 1-(Benzothiazol-2-yl)-4-[(1H)-imidazol-4-yl]piperidine represents a limit structure for H3-activity, since it seems impossible to improve its affinity by means of substitution in the studied position of the benzothiazole nucleus, as shown by predictions performed by a PLS model.

Hyperdynamic left ventricular function and increased left ventricular mass has been recently reported in the long-term follow-up of patients after successful repair of aortic coarctation (AoCo).We studied 35 patients, mean age 22.7 years (range 1-47), following repair of AoCo in order to evaluate: 1) left ventricular mass and systolic function by M-mode echocardiography in comparison with 20 healthy control subjects; 2) the prevalence of systemic hypertension; 3) systolic blood pressure and the trans-isthmic gradient by CW Doppler at rest and after exercise; 4) subjects with a hypertensive response and/or with a significant trans-isthmic gradient during exercise, correlating such parameters with indexes of left ventricular function and the ratio of aortic isthmus/aortic diaphragmatic diameters (AOI/AOD) by means of Magnetic Resonance (MR). At the time of operation, mean age was 12.4 years (range 1 mo-40 yrs) and the follow-up period was 10.1 years (range 6 mo-26 yrs).Left ventricular mass index (Mi) was significantly greater in comparison with that of the controls (96.5 +/- 25 vs 71.5 +/- 16.6 g/m2; p0.001); the mean velocity of circumferential shortening (mVCFc) was increased (1.4 +/- 0.25 vs 1.2 +/- 0.16 circ/s; p0.005); the end systolic meridional stress (ESS) was decreased (37.3 +/- 11.1 vs 47.9 +/- 13.1 g/cm2; p0.005) while the peak systolic meridional stress (PSS) was not significantly different in the two groups. Fourteen out of 35 patients (40%) showed an exaggerated mVCFc for the level of ESS, which indicates an increased inotropic state. Hypertension at rest was present in 10 patients (28%). Mean age at the time of operation of the hypertensive group was higher than that of the normotensive one (21.4 +/- 10 vs 8.9 +/- 8.6 yrs; p0.001). All patients showed a small systolic gradient across the side of coarctation repair at rest (mean 13.1 mmHg; range 0-30). The exercise test was stopped in 5 patients because of hypertension (250 mmHg); 24 patients (80%) showed an exercise-induced hypertension. The mean gradient at maximal exercise was 25.9 mmHg (range 0-52); 6 patients (20%) developed a diastolic gradient. With MR it was possible to evaluate the anatomy of the aortic arch and the descending aorta in all cases. The mean ratio AOI/AOD was 0.81 (range 0.63-1). The age at the time of operation showed a positive correlation with the systolic blood pressure (r = 0.63; p0.001) and with Mi (r = 0.45; p0.005). The systolic blood pressure and the gradient at maximal exercise also showed a positive correlation (r = 0.40; p0.01).In the long-term follow-up of patients after successful coarctation repair there are persistent alterations of left ventricular function with hypertrophy, hyperkinesia and increased inotropic state. Hypertension at rest and after exercise could persist despite good surgical results.

Histamine receptors were characterized in muscle cells isolated from the longitudinal muscle layer of guinea pig intestine. Histamine caused concentration-dependent contraction and stimulated significant increases in [Ca++]i (141 +/- 16 nM, P.001) and cyclic AMP (cAMP) (10.3 +/- 0.5 pmol/10(6) cells, P.001). The H1 receptor antagonist, mepyramine, inhibited contraction and the increase in [Ca++]i, whereas the H2 receptor antagonist, cimetidine, augmented contraction and the increase in [Ca++]i (277 +/- 31 nM, P.01) and abolished the increase in cAMP. In cells maximally contracted with a nonhistamine agonist [cholecystokinin octapeptide (CCK)], histamine caused concentration-dependent relaxation when the contractile effect mediated by H1 receptors was blocked with mepyramine; relaxation was inhibited by cimetidine in a concentration-dependent fashion. The effects mediated by H1 and H2 receptors were characterized further in cells in which only one receptor type was preserved by selective receptor protection. In cells in which only H1 receptors were preserved, histamine caused contraction that was inhibited by mepyramine; no relaxation of CCK-induced contraction could be elicited by histamine in the presence of mepyramine. Conversely, in cells in which only H2 receptors were preserved, histamine had little or no contractile effect by itself but caused relaxation of CCK-induced contraction in the absence of mepyramine. We conclude that in, intestinal muscle cells, H1 receptors mediating Ca(++)-dependent contraction coexist with H2 receptors mediating cAMP-dependent relaxation. The effect of histamine reflects activation of dominant H1 receptors as well as of H2 receptors which act to attenuate [Ca++]i and contraction by stimulating an increase in intracellular cAMP.

The preparation of a representative group of derivatives of the known H3-antagonist thioperamide is described. Binding affinity for histamine H3-receptors of thioperamide and its derivatives, which were obtained by substitution on the imidazole ring, was measured on rat brain cortex synaptosomes. Competitive binding assays were performed with two different labelled ligands, the physiological agonist [3H]histamine ([3H]HA) and the potent H3-agonist N alpha-[3H]methyl-histamine ([3]NAMHA). We observed a remarkable difference in Ki values obtained versus the two labelled ligands, both for thioperamide and its derivatives. In particular, 5-methylthioperamide showed a considerable selectivity for the system recognized by [3H]NAMHA, being about 100 times more potent versus this system than versus the system recognized by [3H]HA. On the basis of these observations, we suggest that it is necessary to consider this difference in evaluating the affinity of new compounds for the H3-receptors.