Association of transition cow health with pregnancy per artificial insemination and pregnancy loss in Holstein cows submitted to a Double-Ovsynch protocol for first service.

This observational study was conducted to evaluate the effect of transition cow health on pregnancy per artificial insemination (P/AI) and pregnancy loss (PL) in cows submitted to a Double-Ovsynch protocol (DO) for first service. Lactating Holstein cows (n = 15,041) from one commercial dairy farm in northern Germany between January 2015 to December 2021 were enrolled into a modified Double-Ovsynch protocol (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 24 h later PGF2α, 32 h later GnRH, and 16 to 18 h later timed artificial insemination) for first service at 72 ± 3 d in milk. Pregnancy was diagnosed at 32 and 60 d post-AI via transrectal ultrasonography. Pregnancy loss was defined as the proportion of cows diagnosed pregnant 32 d post-artificial insemination that were diagnosed nonpregnant 60 d post-artificial insemination. Health-related events (i.e., milk fever [MF], hyperketonemia [KET], retained fetal membranes [RFM], metritis, mastitis, left displaced abomasum [LDA]) were assessed by farm personnel using standard operating procedures. Multivariable logistic regression was used for testing potential associations between transition cow health event occurrence and outcome variables, including P/AI and PL. Three separate models were built for cows in first lactation, second lactation, and ≥third lactation. Overall, 20.0% (885/4,430), 34.9% (1,391/3,989), and 53.9% (3,570/6,622) of cows had at least one transition cow health event for first, second, and ≥third lactations, respectively. The most prevalent transition cow health event for first-lactation cows was metritis (10.7%; [473/4,430]), whereas second-lactation cows suffered mostly from mastitis (16.6%; [664/3,989] and KET (16.6%; [661/3,989]), and cows with ≥third lactations were mostly affected by KET (33.2%; [2,198/6,622]). We observed a negative association between inflammatory disorders (i.e., RFM, metritis, mastitis) and P/AI in all cows irrespective of parity. Metabolic disorders (i.e., MF, KET, LDA) were negatively associated with P/AI only in multiparous cows. Irrespective of parity, only uterine diseases (i.e., RFM, metritis) were significantly associated with PL. These results show that enrolling cows into a fertility protocol, such as DO, cannot overcome the carryover effects of inflammatory and metabolic disorders on P/AI and PL and highlight the importance of optimizing transition cow health as a prerequisite for achieving high fertility in a DO protocol.

Characterization of a PEGylated protein therapeutic by ion exchange chromatography with on-line detection by native ESI MS and MS/MS.

Detailed profiling of both enzymatic (e.g., glycosylation) and non-enzymatic (e.g., oxidation and deamidation) post-translational modifications (PTMs) is frequently required for the quality assessment of protein-based drugs. Challenging as it is, this task is further complicated for the so-called second-generation biopharmaceuticals, which also contain "designer PTMs" introduced to either enhance their pharmacokinetic profiles (e.g., PEGylated proteins) or endow them with therapeutic activity (e.g., protein-drug conjugates). Such modifications of protein covalent structure can dramatically increase structural heterogeneity, making the very notion of "molecular mass" meaningless, as ions representing different glycoforms of a PEGylated protein may have nearly identical distributions of ionic current as a function of m/z, making their contributions to the mass spectrum impossible to distinguish. In this work we demonstrate that a combination of ion exchange chromatography (IXC) with on-line detection by electrospray ionization mass spectrometry (ESI MS) and methods of ion manipulation in the gas phase (limited charge reduction and collision-induced dissociation) allows meaningful structural information to be obtained on a structurally heterogeneous sample of PEGylated interferon ß-1a. IXC profiling of the protein sample gives rise to a convoluted chromatogram with several partially resolved peaks which can represent both deamidation and different glycosylation patterns within the protein, as well as varying extent of PEGylation. Thus, profiling the protein with on-line IXC/ESI/MS/MS allows it to be characterized by providing information on three different types of PTMs (designer, enzymatic and non-enzymatic) within a single protein therapeutic.

A protective role for IL-13 receptor α 1 in bleomycin-induced pulmonary injury and repair.

Molecular mechanisms that regulate lung repair vs. progressive scarring in pulmonary fibrosis remain elusive. Interleukin (IL)-4 and IL-13 are pro-fibrotic cytokines that share common receptor chains including IL-13 receptor (R) α1 and are key pharmacological targets in fibrotic diseases. However, the roles of IL-13Rα1 in mediating lung injury/repair are unclear. We report dysregulated levels of IL-13 receptors in the lungs of bleomycin-treated mice and to some extent in idiopathic pulmonary fibrosis patients. Transcriptional profiling demonstrated an epithelial cell-associated gene signature that was homeostatically dependent on IL-13Rα1 expression. IL-13Rα1 regulated a striking array of genes in the lung following bleomycin administration and Il13ra1 deficiency resulted in exacerbated bleomycin-induced disease. Increased pathology in bleomycin-treated Il13ra1(-/-) mice was due to IL-13Rα1 expression in structural and hematopoietic cells but not due to increased responsiveness to IL-17, IL-4, IL-13, increased IL-13Rα2 or type 1 IL-4R signaling. These data highlight underappreciated protective roles for IL-13Rα1 in lung injury and homeostasis.

Effect of topical anti-inflammatory treatment on the long-term outcome of laser trabeculoplasty. Fluorometholone-Laser Trabeculoplasty Study Group.

PURPOSE: To investigate the effect of anti-inflammatory treatment on the long-term outcome of argon laser trabeculoplasty, we extended the short-term study of the Fluorometholone-Laser Trabeculoplasty Study Group. METHODS: Among the chronic open-angle glaucoma patients randomly assigned to the 0.25% fluorometholone or placebo eyedrops four times daily before and after argon laser trabeculoplasty in the Fluorometholone-Laser Trabeculoplasty Study, the long-term records of 27 patients (13 eyes in the fluorometholone group and 14 eyes in the placebo group) were available for our review and analysis. RESULTS: There were no statistically significant differences in the success rate of argon laser trabeculoplasty between the fluorometholone and control groups over the follow-up period of 4.6 +/- 3.4 years. CONCLUSION: While it decreased ocular inflammation and discomfort during the early postoperative period, peri-argon laser trabeculoplasty use of a topical corticosteroid did not influence the long-term intraocular pressure outcome of argon laser trabeculoplasty.

Laser trabeculoplasty: how little is enough?

BACKGROUND AND OBJECTIVE: The optimal number of laser applications for argon laser trabeculoplasty in patients with primary open-angle glaucoma has not been established. The purpose of this study was to determine the fewest number of burns necessary for clinically effective intraocular pressure reduction for these patients. PATIENTS AND METHODS: Using a prospective, randomized, collaborative study, the authors examined the relationship between the number of laser trabeculoplasty burns and intraocular pressure for patients with primary open-angle glaucoma. A total of 122 patients received either 50 burns to half of the trabecular meshwork (group 1) or 35 burns to one third of the trabecular meshwork (group 2). RESULTS: The mean baseline intraocular pressures were similar between group 1 (22.3 +/- 4.1 mm Hg [mean +/- SD]) and group 2 (22.8 +/- 5.0 mm Hg) (P = .58). Intraocular pressure reduction at 9 to 12 months, although significant in both groups (group 1: 4.4 +/- 3.0 mm Hg, P < .0001; group 2: 3.9 +/- 5.1 mm Hg, P < .0001), did not differ significantly between the two groups (P = .63). CONCLUSION: This study demonstrated that 35 burns may be as clinically effective as 50 burns in reducing the intraocular pressure in primary open-angle glaucoma patients.

Effect of dexamethasone on rat plasma platelet activating factor acetylhydrolase during the perinatal period.

It has been previously reported that the administration of dexamethasone (DEX) to adult rats increases the activity of plasma platelet-activating factor acetylhydrolase (PAF-AH) and prevents the development of intestinal necrosis caused by platelet activating factor (PAF) injection. In this report, we examined the effect of DEX administration on plasma PAF-AH activity during the perinatal period. Timed-pregnant rats received DEX (0.2-1.0 mg/kg/d) or normal saline (controls) on days 16-18 (early group) or days 18-20 (late group) of gestation. Maternal plasma PAF-AH activity was lower in late gestation than in postpartum period (P < 0.001). Fetal and neonatal plasma PAF-AH activity was higher than maternal values (P < 0.05). No changes of PAF-AH activity were seen in maternal, fetal or neonatal plasma after prenatal DEX administration at the aforementioned doses. A higher dose of DEX (1.3 mg/kg/d x 4d) or cortisone (200 mg/kg/d) produced an elevation of maternal plasma PAF-AH activity (DEX 79.2+/-3.0, cortisone 70.5+/-1.9 vs. controls 49.4+/-2.3 nmol/min/ml, P < 0.01), but resulted in a high fetal mortality. Treatment of newborn rats with DEX (0.5 mg/kg/d) on days 1-3 after birth, increased plasma PAF-AH activity on day 4 (DEX 292+/-5 versus controls 140+/-9 nmol/min/ml, P < 0.001) and day 6 (DEX 302+/-12 versus controls 136+/-6 nmol/min/ml, P < 0.001). Postnatal administration of DEX increases the plasma PAF-AH activity in the rat. Only high doses of prenatal corticosteroids that cause fetal death can elevate maternal plasma PAF-AH activity.

Effect of topical anti-inflammatory treatment on the outcome of laser trabeculoplasty. The Fluorometholone-Laser Trabeculoplasty Study Group.

PURPOSE: We investigated the effect of anti-inflammatory treatment on the outcome of argon laser trabeculoplasty. METHODS: In this multicenter, double-masked, randomized, placebo-controlled, parallel comparison study, 140 chronic open-angle glaucoma patients received either 0.25% fluorometholone or vehicle four times a day unilaterally, beginning 24 hours before and continuing one week after argon laser trabeculoplasty. The laser surgeon placed 50 to 60 burns over the inferior 180 degrees of the trabecular meshwork. The patients were followed up frequently for five weeks after the procedure. RESULTS: Following argon laser trabeculoplasty, signs of anterior chamber inflammation were significantly lower in the fluorometholone group. However, there was no significant difference between the fluorometholone and the vehicle groups in the incidence of increased intraocular pressure in the immediate post-argon laser trabeculoplasty period. Intraocular pressure decreased significantly in both groups from day 1 throughout the follow-up period. A significant between-group difference in intraocular pressure decrease was found only at week 5 (7.83 +/- 6.27 [S.D.] mm Hg for the fluorometholone group vs 6.63 +/- 5.79 mm Hg for the vehicle group, P = .046). No drug-related clinically significant adverse events were observed. CONCLUSIONS: Use of fluorometholone is effective in attenuating inflammation and has no clinically significant impact on the outcome of argon laser trabeculoplasty or on the incidence of intraocular pressure spikes during the immediate post-argon laser trabeculoplasty period.

Changes in glycerophospholipid profile in experimental nephrotic syndrome.

We investigated changes in the glycerophospholipids in kidney tissue and its various intracellular fractions in rats with nephrotic syndrome induced by puromycin aminonucleoside. The ethanolamine plasmalogen, 1-O-alk-1'-enyl-2-acyl-GPE (EP), was increased in kidney tissue obtained from the puromycin-treated animals. A similar increase was found in the mitochondria and endoplasmic reticulum (microsomes) of this tissue. These increases were not found in the liver. Since platelet-activating factor (PAF) is known to be produced in increased amounts in inflammatory disorders, it is suggested that the higher plasmalogen found in rat kidneys during experimental nephrotic syndrome might be derived from increased levels of this autacoid. The increase in PAF may also result in the elevation of plasma PAF-acetylhydrolase (AH) activity observed in these animals.

The biochemical role of platelet-activating factor in reproduction.

The presence of Co-A independent transacylase activity in amnion cells and the preferential transfer of arachidonic acid to acceptor-ethanolamine plasmalogen provide a satisfactory explanation to the questions raised by the observation that arachidonate-enriched ethanolamine plasmalogen increases in amnion late in gestation without alteration in the total amount of ethanolamine glycerophospholipids. The proposed mechanism also serves as a link between the observed changes in glycerophospholipid composition and the generation of PAF. We have emphasized a role for PAF in fetal lung maturation, the initiation and maintenance of parturition, and in certain complications associated with a premature delivery. Although PAF is known to be the most potent lipid mediator yet described and its importance in reproductive biology is well documented, it is our view that these events cannot be attributed solely to PAF and in all likelihood a number of autacoids participate in these processes.

Oedipal and preoedipal transference transformations. Comments on the analysis of a latency-age boy.

The critical importance of both oedipal and preoedipal unconscious conflicts in child and adult analysis as these conflicts unfold through the transference is documented using analytic process data. Evidence is provided that demonstrates the equal relevance of these psychic conflicts and their continuous interactions. The concept of transference transformations is proposed to explain these and later psychic conflicts that are resolved through the mutative interpretations unique to psychoanalysis. Extensive clinical data from the analysis of a latency-age boy are presented in support of this thesis. Thus, transference neurosis that arises from the infantile neurosis, the structural residue of the Oedipus complex, would be subsumed within the group of transference transformations. This concept eliminates the obligation to emphasize one developmental phase over another.

A reconsideration of object choice in women: phallus or fallacy.

Within the context of Freud's theory of instinctual drives, analytic data from three female patients are presented which refute his concept that penis envy is the basis for female object choice. Contrary to Freud's theory, these patients did not feel their genitalia or genital arousal were inadequate. Rather, they believed their genital sexuality and fantasies were powerful and gratifying, but dangerous and bad. Their subsequent guilt and fears led secondarily to their defensive wish to have a penis to avoid their core conflicts; their penis envy was pathological. The data unequivocally demonstrate that the clitoris is not an inferior organ, but is the locus for the initiation of intense pleasure and occasional orgasm as early as ages four to six, when vaginal awareness also is present. In addition the material provides evidence that girls choose fathers to feel loved and valued, and that their wish for a baby is not a substitute for a relinquished wish for a penis. Observational studies and a vignette suggest that the instinctual drives of the genital phase coalesce with a change in object relations, forming an important motivation for a girl to switch her primary love object from her mother to her father.

Evaluación clínica del vello corporal en mujeres sanas / Clinical assessment of body hair in healthy women

To study tha amount and distribution of terminal body hair in non-hirsute women consulting in a public outpatient clinic. Two hundred thirty six premenopausical women consulting in a birth control clinic or consulting for acute non-endocrinological diseases were studied. Body hair was assessed with a semi-quantitative clinical method described by Ferriman and Gallwey. Ninetyfive percent of women had a score equal or less than 5. No correlations were found between the score and body mass index or age. Partial scores over 1 were found specially in the lower abdomen, chest, superior lip and thighs. This sample of women, coming from middle and low socioeconomic levels, appears more hairlee than European or North American Women. Thus, hirsutism must be suspected with scores over 5. These results cannot be extrapolated to all Chilean women, due to differences in ethnical backgrounds

Nocardiosis diseminada en tres pacientes inmunocompetentes / Disseminated nocardiosis in 3 immunocompetent patients

Nocardia asteroide infections, an aerobic actinomycete, have several forms and lungs, skin and brain are the organs most frequently involved. When the infection suspected, special staining methods must be ordered to identify the agent. We report three immunocompetent patients with disseminated nocardiosis, 2 presenting with nodular lesions of skin and lungs and one presenting with pulmonary involvement and brain abscesses. The importance of clinical suspicion and early diagnosis of nocardiosis is emphasized

Platelet-activating factor. Role in fetal lung development and relationship to normal and premature labor.

In this overview on the role of PAF in reproductive biology, we have emphasized its relationship to fetal lung maturation and the initiation and maintenance of parturition. In addition, we have discussed the role of this autacoid in certain complications of premature delivery. It should be pointed out, however, that it is our view that other mediators and cytokines also play a role in these processes. In the past, many investigators have suggested a central role for one of these mediators that serves as the "trigger" of these biologic events. It is our view that these systems are regulated by a number of effectors, among which PAF may play an important role.

Metabolic fate of platelet-activating factor in the rat enterocyte: the role of a specific lysophospholipase D.

The metabolism of platelet-activating factor (PAF) by isolated rat intestinal epithelial cells was investigated using 1-[3H]octadecyl-2-acetyl-sn-glycero-3-phosphocholine. The principal metabolite produced by the cells was 1-O-alkylglycerol, which was found in association with the cells and the medium. When similar studies were conducted employing an intestinal epithelial cell line (INT 407), PAF was almost quantitatively converted into 1-alkyl-2-acyl-sn-glycero-3-phosphocholine (AAGPC). When the intestinal epithelial cell microsomes were incubated in the presence of fluoride to inhibit phosphohydrolase activity, the formation of 1-alkylglycerol was decreased in association with a stoichiometric increase in 1-alkyl-glycerophosphate, indicating the presence of a lysophospholipase D in the intestinal cells. When the phospholipase D activity was examined in the microsomal fraction prepared from intestinal epithelial cells, lyso-PAF was the preferred substrate and only trace amounts of lyso-PAF were converted into alkylacyl-GPC. Acyllyso-GPC was rapidly cleaved to form free fatty acids. The absence of lysophospholipase D activity in INT 407 cells cannot be attributed to the absence of brush border in these cells since no lysophospholipase D activity was present in isolated brush border preparations.

[Action of Buflomedil on the cutaneous microcirculation studies by a cold provocation test. Multicenter, double-blind, placebo controlled trial]. / Action du Buflomédil sur la microcirculation cutanée étudiée par un test de provocation au froid. Etude multicentrique, double aveugle versus placebo.

The aim of this multicentre trial involving 136 cardiologists was to evaluate, in double-blind versus placebo design, the vasoactive effect of Buflomedil in out-patients with a very simple cooling-test from a practical standpoint and previously described (1). The authors have selected patients having a basal pulpar temperature below 30 degrees C by cutaneous thermometer and falling after immersion of the contralateral hand in water at 4 degrees C, with out complete recovery during 10 minutes following withdrawal. This study carried out 408 eligible patients with 398 finally included in double-blind period (200 in the Buflomedil group, 198 in the placebo group). After a run-in period of 7 days with placebo in single blind, to evaluate the stability of measures, the patients were then treated with either Buflomedil 600 mg a day or placebo at the same dosage, for 14 days. The patients in both groups had a Raynaud's phenomenon and were heavy smokers (> or = 20 packs/year), having either acrocyanosis or lower limbs arterial occlusive disease. The results have shown, after 14 days of oral treatment an increase of basal temperature of 2.01 degrees C in Buflomedil group, versus only 0.82 degrees C in placebo group. This warming-up give evidence of microcirculatory blood flux increasing. This significant difference between the both groups was the same each measurement time after immersion during the recovery phase. There also was a good parallelism between the cutaneous temperature and the global clinical improvement by visual analogic scale filled out by the investigator (p < or = 0.0001) and the patients (p < or = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Cutaneous pulpar temperature and cold test. Predictive specificity and sensitivity in pharmaco-clinical studies]. / Température cutanée pulpaire et test au froid. Spécificité et sensibilité prédictives en pharmacoclinique.

The aim of this study was to measure the cutaneous pulpar temperature of the fingers and assess its evolution after one minute of controlateral hand immersion in a water bath at 4 degrees C and during 10 minutes after cooling. This test was carried out in 347 subjects (120 M, 227 F) divided in 5 groups: 117 healthy volunteers (49 M, 68 F) without any vascular diseases, 46 patients (5 M, 41 F) with acrocyanosis, 87 patients (19 M, 68 F) with Raynaud's phenomenon, 31 patients (24 M, 7 F) with peripheral arterial occlusive disease and 66 patients (23 M, 43 F) with other vascular diseases (high blood pressure and coronary disease). The mean initial temperature (TO) analysis in each group, showed that 2 groups, acrocyanosis and especially Raynaud's group, had a finger temperature significantly lower than the control group (27.4 +/- 4.8 degrees C 25.3 +/- 4.9 degrees C versus 30.5 +/- 4.9, p < 0.02). The cooling test showed 3 different cutaneous temperature reactions: subjects without any modification during and after immersion, subjects with a temperature decreasing after immersion and a normal rewarming after 10 minutes and subjects with a decreasing without any total recovery after 10 minutes. In the subjects with cold hands (initial temperature < 30 degrees C), this cooling test can isolate all patients with a temperature decreasing without any rewarming after 10 minutes with a specificity at 100% (no normal subject with cold hands were abnormal to this test).(ABSTRACT TRUNCATED AT 250 WORDS)

Coenzyme A-independent transacylation in amnion-derived (WISH) cells.

Total membranes or microsomal fractions prepared from the amnion-derived WISH cell line posses a coenzyme A-independent transacylase activity. The transacylase utilizes 1-alkenyl- and 1-alkyl-2-lysoglycerophospholipids as preferred acceptors. Marginal transacylation was observed with 1-acyl-2-lysoglycerophospholipids. The reaction occurred in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and was not affected by phospholipase A2 inhibitors. Both 1-acyl- or 1-alkyl-glycerophosphocholines containing an arachidonoyl residue in the sn-2 position were effective as donors, while 2-oleoyl- or 2-palmitoyl-glycerophosphocholines were ineffective. The presence of the transacylase, the specificity of the substrates, and the stability of the 1-alkenyl bond provide a biochemical model that may explain the increased proportion of a highly enriched arachidonate-containing phosphatidyl-ethanolamine-plasmalogens fraction that is found in amnion at term.