Fertility and survival of Swedish Red and White × Holstein crossbred cows and purebred Holstein cows.

Swedish Red and White × Holstein (S×H) cows were compared with pure Holstein (HOL) cows for fertility and survival traits in 2 commercial dairy farms in central-southern Córdoba province, Argentina, over 6 years (2008-2013). The following traits were evaluated: first service conception rate (FSCR), overall conception rate (CR), number of services per conception (SC), days open (DO), mortality rate, culling rate, survival to subsequent calvings, and length of productive life (LPL). The data set consisted of 506 lactations from 240 S×H crossbred cows and 1,331 lactations from 576 HOL cows. The FSCR and CR were analyzed using logistic regression, DO and LPL were analyzed using a Cox's proportional hazards regression model, and differences of proportions were calculated for mortality rate, culling rate, and survival to subsequent calvings. The S×H cows were superior to HOL cows in overall lactations for all the fertility traits (+10.5% FSCR, +7.7% CR, -0.5 SC, and 35 fewer DO). During the first lactation, S×H cows were superior to HOL cows for all fertility traits (+12.8% FSCR, +8.0% CR, -0.4 SC, and 34 fewer DO). In the second lactation, S×H cows exhibited lower SC (-0.5) and 21 fewer DO than HOL cows. In the third or greater lactations, S×H cows showed higher FSCR (+11.0%) and CR (+12.2%), lower SC (-0.8), and 44 fewer DO than pure HOL cows. In addition, S×H cows had a lower mortality rate (-4.7%) and a lower culling rate (-13.7%) than HOL cows. Due to the higher fertility and lower mortality and culling rates, the S×H cows had higher survival to the second (+9.2%), third (+16.9%), and fourth (+18.7%) calvings than HOL cows. Because of these results, S×H cows had longer LPL (+10.3 mo) than HOL cows. These results indicate that S×H cows had higher fertility and survival than HOL cows on commercial dairy farms in Argentina.

Modeling variability of the lactation curves of cows in automated milking systems.

Historically, cow selection criteria were developed for conventional milking systems that have regular milking intervals (MI). However, in automatic milking systems (AMS), there is variability in MI within and between cows. These sources of variability provide an opportunity to identify cows with high daily milk yield (DY) and long MI. An extended MI (longer than 16 h in pasture-based systems) has a negative effect on DY. Cows that tolerate extended MI and maintain high DY can be considered more efficient than cows with low DY and long MI, or with high DY but short MI, thereby improving robotic system use. Knowledge of the behavior and parameters of lactation curves of cows in AMS could help farmers to identify cows with a specific lactational phenotype. The objective of this study was to identify individual cows with high DY and long MI within herds, which could reflect increased tolerance to milk accumulation under AMS. A database containing records for 773,483 milking events for one year (July 2016-June 2017) from 4 pasture-based AMS farms was used. Lactation curves within each herd were fitted using several mixed models including fixed effects for the parameters of the lactation curve and random cow effects. Predicted curves of average DY according to parity (multiparous and primiparous) were obtained. The best linear unbiased prediction of the random cow effect allowed us to categorize lactations as having either high or low milk production. The median MI of each lactation was then used to categorize cows as having either short or long MI. Daily yield at the peak of lactation, days to peak and 305-d cumulative milk production were used to compare the effect of DY and MI categories, as well as the DY × MI interaction. Milk production by multiparous and primiparous cows with high DY and long MI was between 35 and 45% higher than that of the low DY and short MI. From all lactations analyzed, the incidence of animals with high DY and long MI across farms was 7.5%. We have identified and quantified a new, AMS-specific, phenotype (the combination of a relatively higher DY with relatively longer MI) with potential to increase use of AMS units. Identifying more efficient animals should help generate new approaches for differential management and for selecting cows in AMS.

Effect of puerperal metritis on reproductive and productive performance in dairy cows in Argentina.

The objectives of this study were to evaluate the reproductive and productive performance of dairy cows with and without puerperal metritis and to evaluate the effectiveness of using a long-acting ceftiofur preparation. Dairy cows in one dairy farm, calving from July 2009 to January 2010, were examined between 3 and 14 days postpartum and classified on the basis of vaginal discharge into three groups: cows with normal discharge (control; C); cows with a bloody mucus purulent or pathologic nonfetid discharge (PnFD), and cows with bloody mucopurulent or purulent fetid discharge (PFD). Cows in C and PnFD groups were not treated, whereas those in the PFD group were randomly allocated to receive 2.2 mg/kg of ceftiofur subcutaneously behind the ear (PFD-T) or remain untreated (PFD-No T). From the 640 cows examined, 58.2% formed the C group, 13.4% formed the PnFD group, and 28.4% formed the PFD group. Survival curves differed between cows in the C group and PFD-No T group (P = 0.0013) and between PFD-No T versus PFD-T group (P = 0.0006). Survival curves of PnFD were intermediate and did not differ from those in the C group (P = 0.2) and PFD-T group (P = 0.1) but tended to be different from the PFD-No T group (P = 0.056). The postpartum interval to achieve a 25% pregnancy rate was 72 days for cows in the C group, 73 days for the PFD-T group, 83 days for PnFD group, and 95 days for the PFD-No T group. The chance of pregnancy in a cow in the C group was 1.98 times higher (95% confidence interval = 1.33, 3.08) and in cows in the PFD-T group was 2.16 times higher (95% confidence interval = 1.37, 3.50) than that in the PFD-No T group. Finally, the chance of pregnancy in cows in the PnFD group tended to be higher (P = 0.08) than that in the PFD-No T group but did not differ from the other two groups. Cumulative 305-day milk production was higher (P < 0.0001) in C group than those with vaginal discharge, regardless of fetidness and regardless of treatment. It is concluded that puerperal metritis affects the reproductive and productive performance of dairy cows and the treatment with ceftiofur was effective in reducing the adverse effects on reproductive performance but not on milk production.

Some factors affecting the number of days open in Argentinean dairy herds.

The objective of this study was to estimate the relative contribution of factors affecting how quickly cattle become pregnant in Argentine dairy herds. Data from 76,401 cows from 249 dairy herds were analyzed. A hazard model was used to explore days open (DO). The factors considered were milk yield, lactation number, calving season, and breeding technique (i.e., type of service: artificial insemination [AI], or combined service). Cows with lower milk yield had 1.09 to 1.38 higher likelihood to become pregnant than those with higher milk yield (P < 0.0001). The number of DO increased linearly with an increasing number of lactations (P < 0.0001). Cows calving in fall-winter had a shorter interval to conception than those calving in summer. The hazard rate for combined service was 1.27; therefore, cows with combined service were more likely to become pregnant during the observation period than those bred by AI. The difference in DO between cows of high versus low milk yield was smaller when dairies used AI as the main breeding technique than when they used combined service. Furthermore, dairies using mainly combined service had lower milk yield (5693.7 L) than those using mainly AI (7684.4 L). Although lactation number and calving season contributed to explain the number of DO, the influence of production level, the type of service, and the interaction between them was also associated with reproductive efficiency in Argentine dairy herds.

A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function.

Objectives. In a previous randomized clinical trial (Falsini et al. (2010)), it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration. Design. Longitudinal, interventional open-label study. Setting. Outpatient ophthalmology setting. Participants. Twenty-nine early AMD patients (age range: 55-85 years) with a baseline visual acuity >0.3. Intervention. Saffron oral supplementation (20 mg/day) over an average period of treatment of 14 (±2) months. Measurements. Clinical examination and focal-electroretinogram-(fERG-) derived macular (18°) flicker sensitivity estimate (Falsini et al. (2010)) every three months over a followup of 14 (±2) months. Retinal sensitivity, the reciprocal value of the estimated fERG amplitude threshold, was the main outcome measure. Results. After three months of supplementation, mean fERG sensitivity improved by 0.3 log units compared to baseline values (P < 0.01), and mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, P < 0.01). These changes remained stable over the follow-up period. Conclusion. These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term followup.

Retinal sensitivity to flicker modulation: reduced by early age-related maculopathy.

PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. RESULTS: In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.

Family-based association study between bipolar disorder and DRD2, DRD4, DAT, and SERT in Sardinia.

Association analysis of candidate genes may represent a strategy for clarifying the genetic components involved in bipolar disorder. Polymorphism at dopamine receptor genes DRD2, DRD4, and dopamine and serotonin transporter genes (DAT, SERT) has been used in previous association studies. Some authors have reported positive association between certain alleles and bipolar disorder, using the case-control design. In this family-based association study of DRD2, DRD4, DAT, and SERT, the distribution of parental nontransmitted alleles was compared with that of alleles transmitted to 53 Sardinian probands suffering from bipolar disorder. The transmission disequilibrium test (TDT) was used to detect any disproportionate transmission of alleles by heterozygous parents to affected children. No differences were found between the allele distribution of polymorphisms at DRD2, DRD4, DAT, and SERT in probands and parental nontransmitted chromosomes. TDT did not reveal any difference between transmitted and nontransmitted alleles. Our results do not support the hypothesis of a role for DRD2, DRD4, DAT, or SERT in bipolar disorder. Previously reported positive associations between DRD2 or SERT and bipolar disorder were conceivably due to stratification dependent on the case-control design, even though our sample might have failed to detect small associations due to limited power.

The fundamental and second harmonic of the photopic flicker electroretinogram: temporal frequency-dependent abnormalities in retinitis pigmentosa.

OBJECTIVES: The flicker electroretinogram (FERG) consists mainly of a linear (fundamental, 1F) and a non linear (second harmonic, 2F) component. Previous results indicate that 2F originates more proximally in the retina than 1F, and that retinitis pigmentosa (RP) may affect 2F to a greater extent than 1F. The aim of this study was to evaluate FERG 1F and 2F abnormalities in RP as a function of the stimulus temporal frequency (TF). METHODS: Twelve patients with typical RP and 10 age-matched controls were examined. FERGs were recorded in response to uniform fields (18 degrees) presented in the macula on a light-adapting background. Stimuli were flickered sinusoidally at different, closely spaced TFs between 3.7 and 52 Hz. Amplitudes and phases of the Fourier analysed 1F and 2F components were measured. Components' apparent latencies were estimated from the rate at which phase lagged with TF. RESULTS: When compared to controls, mean 1F amplitudes of patients were reduced at both low (3.7-12.6 Hz) and high (14-52 Hz) TFs, with greatest losses (0.5 log units) around the peaks (3.7 and 41 Hz) of the normal TF function. Mean 2F amplitudes were reduced mainly at low TFs, with greatest losses (0.5 log units) at 5-8 Hz. On average, the shape of the 2F, but not 1F amplitude versus TF function, differed between patients and controls, showing a selective attenuation at low TFs. Mean 1F apparent latencies were delayed at both low and high TFs, with greater delays at low (85 ms) than at high (33 ms) TFs. Mean 2F apparent latencies were delayed only at low TFs (58 ms). CONCLUSIONS: In RP, 1F and 2F phase delays as well as 2F amplitude losses are dependent on TF, suggesting that FERG generators' subpopulations in both distal and proximal retina are differentially affected. Analysis of the FERG TF response is potentially useful to characterize cone system dysfunction in different genetic subtypes of RP.

Maternal inheritance of manic depression in hemizygotes for the G6PD-Mediterranean mutation. Indirect evidence for Xq28 transmission in Sardinia.

Both X-linkage and a parent-of-origin effect have been hypothesized in manic-depressive disorder. We have previously shown an allelic association between X-linked G6PD deficiency and manic depression in Mediterranean populations. To test both X-linkage and a parent-of-origin effect in manic depression further, we have studied 274 Sardinian manic-depressive probands and their parents. Excess of maternal transmission (P = 0.005) of major affective disorder was found in male probands carrying the G6PD-Mediterranean mutation. Our results provide indirect molecular support for an association between manic depression and the Xq28 chromosome region in Sardinia. Further studies on Xq28 using tests of allelic association and transmission disequilibrium with multiple DNA markers are required, to clarify the nature of the association we have found. Our study cannot implicate or exclude a direct role for G6PD deficiency in the aetiology of manic depression.

The spatial tuning of steady state pattern electroretinogram in multiple sclerosis.

In normal subjects, the steady-state electroretinogram in response to contrast reversing gratings (PERG), is spatially band-pass tuned in amplitude, with a maximum at intermediate spatial frequencies and an attenuation at lower and higher ones. The amplitude attenuation at low spatial frequencies is believed to reflect centre-surround antagonistic interactions in the receptive fields of inner retinal neurons. The aim of this study was to evaluate the PERG spatial tuning in multiple sclerosis (MS) patients without a previous optic neuritis history. Steady- state PERGs in response to counterphase-modulated (8 Hz) sinusoidal gratings of variable spatial frequency (0.6, 1.0, 1.4, 2.2 and 4.8 c/deg), were recorded from 18 patients with definite or probable MS and no history of optic neuritis (ON-). Nine of them had no signs of subclinical optic nerve demyelination (asymptomatic) in either eye, while nine had symptoms or signs of optic pathways involvement (symptomatic) in one or both eyes. Results were compared with those obtained from 10 MS patients with a previous history of optic neuritis (ON+) in one or both eyes, as well as from 21 age-matched controls. The amplitudes and phases of the responses' 2nd harmonics were measured. Compared with the controls, asymptomatic ON- patients showed selective losses in mean PERG amplitudes at medium and high (1.0-4.8 c/deg) spatial frequencies. Symptomatic ON- patients and ON+ patients had reductions in mean PERG amplitudes, with respect to controls, involving the whole spatial frequency range, but with greater losses at medium-high (1.0-4.8 c/deg) than at lower spatial frequencies. In all patients' groups, the average PERG spatial tuning function differed significantly from that of the controls, assuming a low-pass instead of the normal band-pass shape. The PERG phase was delayed in ON+ but not in ON- patients, as compared to controls. However, the phase delay was independent of spatial frequency. In both ON- and ON+ patients, losses in PERG amplitude and spatial tuning tended to be associated with corresponding abnormalities in perimetric sensitivity, visual acuity, colour vision and transient visual evoked potential (VEP) latency. The results indicate that abnormalities of the spatial tuning of steady-state PERG can be found in MS patients without either optic neuritis or signs of subclinical optic nerve demyelination. These changes may reflect a retinal dysfunction, developing early in the course of MS, due to a loss of specific subpopulations of inner neurons, changes in lateral interactions of their receptive fields, or both.

Association between dopamine receptor genes and migraine without aura in a Sardinian sample.

BACKGROUND: Migraine seems to be caused by a combination of environmental and genetic factors. Clinical and pharmacologic evidence supports the hypothesis that dopaminergic transmission is involved in the pathogenesis of migraine. OBJECTIVE: The current report concerns a genetic study to test the involvement of genes for dopamine (DA) receptors D2 (DRD2), D3 (DRD3), and D4 (DRD4) in migraine without aura, particularly in a subgroup with enhanced DA sensitivity. METHODS: For the first time, a family-based association method--the Transmission Disequilibrium Test (TDT)--was used to examine an isolated population, such as Sardinians. We studied 50 nuclear families of patients affected by migraine without aura. The subgroup of dopaminergic migraineurs was selected based on the presence of both nausea and yawning immediately before or during the pain phase of migraine. RESULTS: No association was detected using the TDT between DRD3, DRD4, and migraine without aura either in the overall sample or in the subgroup. No difference was observed in DRD2 allelic distribution in the overall sample, although the allelic distribution at the DRD2 locus differed significantly in the subgroup of dopaminergic migraineurs (p = 0.004). Allele 1 of the TG dinucleotide intronic noncoding polymorphism of the DRD2 locus was the individual allele that appeared to be in disequilibrium with migraine without aura (p = 0.02). CONCLUSIONS: Our data suggest that a genetic approach could be useful in providing molecular support to the hypothesis that hypersensitivity of the dopaminergic system may represent the pathophysiologic basis of migraine, at least in a subgroup of patients.

No evidence of association between dopamine D3 receptor gene and bipolar affective disorder.

A recent study reported a possible association between allele 1 of the dopamine D3 receptor gene and bipolar affective disorder using the haplotype relative risk approach. In attempt to replicate these findings, we used similar family-based methods, such as the Haplotype-Based Haplotype Relative Risk method and the Transmission Disequilibrium Test, in a sample of 44 bipolar probands from Sardinia with both parents available. Using the Bal I restriction enzyme site polymorphism of Lannfelt et al. (1992), no differences were found between transmitted and non-transmitted alleles and no evidence of linkage disequilibrium was observed.

Heterogeneity of monoaminergic vesicular carriers: pharmacological evidence using MPP+ as a marker.

MPP-production and uptake by dopaminergic terminals are critical steps in MPTP-induced Parkinson-like disorder. We reported evidence for a specific uptake of MPP by synaptic vesicles from mouse striatum. Its regional distribution suggests it as a marker of the dopamine vesicular carrier. We decided to further characterize such an MPP uptake. Tetrabenazine inhibits the dopamine uptake both in the striatum and in the cerebellum with similar Km values suggesting an identify of the vesicular carrier in these areas. On the contrary, 3H-MPP vesicular uptake had in the striatum a t1/2 of 60 sec, but was not detectable at any time in the cerebellum. Moreover, MPP inhibited the uptake of 3H-DA (Ki: 1.6 +/- 0.03 microM) and 3H-NE (Ki 2.6 +/- 0.01 microM) in the striatum but not in the cerebellum, even at molar concentration. These pharmacological data indicate that in nondopaminergic areas the monoamine carrier may be similar but not identical from that located in dopaminergic areas.

Detection of glaucomatous damage in patients with osteo-odontokeratoprosthesis.

BACKGROUND: Osteo-odontokeratoprosthesis (OOKP) is an autologous transplantation procedure in which the cornea is replaced by an optical cylinder glued to a biological support. Patients undergoing OOKP surgery may develop a secondary glaucoma whose diagnosis, by means of standard diagnostic procedures, is often doubtful. METHODS: In the present study pattern electroretinograms (PERGs), visual evoked potentials (VEPs), contrast sensitivity, and automated threshold perimetry (Humphrey 30-2) were evaluated in 19 OOKP treated patients with postoperative visual acuities > or = 0.8. Nine patients had had a preoperative secondary glaucoma, while the remaining 10 had no history of glaucoma and normal posterior pole. RESULTS: Results were compared with those obtained from either normal control subjects or from ordinary glaucoma patients. PERG amplitudes and contrast and perimetric sensitivities were reduced in both groups of OOKP patients when compared with normal controls. However, these losses were significantly greater in OOKP patients with glaucoma compared with those with normal posterior pole. VEPs were reduced, compared with controls, only in OOKP patients with glaucoma. These VEP losses were similar to those found in ordinary glaucoma patients. CONCLUSION: Among the tests employed, VEPs showed the best accuracy (79%) in discriminating between glaucomatous and non-glaucomatous OOKP treated eyes. The present results suggest a possible use of the VEP technique for detecting glaucomatous dysfunction after OOKP.

In brown Norway rats, MPP+ is accumulated in the nigrostriatal dopaminergic terminals but it is not neurotoxic: a model of natural resistance to MPTP toxicity.

Rats have been described as being insensitive to relatively high doses of systemically administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that in primates induces a neurological syndrome identical to idiopathic Parkinson's disease. The current explanation for the rat resistance is that most of the MPTP is converted into the toxic metabolite 1-methyl-4-phenylpyridium (MPP+) by the MAO-B present in the brain vessel endothelium. Since MPP+ is a polar compound, a very low amount could cross the blood-brain barrier and be present inside the brain. We administered C57 BL mice and Brown Norway rats with either MPTP (30 mg/kg, ip) or the combined treatment MPTP + diethyldithiocarbamate (DDC). In mice, DDC prolonged the striatal exposure to MPP+, potentiated the MPTP-induced acute syndrome, and enhanced the MPTP-induced striatal dopamine depletion. In rats, DDC potentiated the MPTP-induced acute syndrome, but no changes in the striatal dopamine were observed after either MPTP or DDC + MPTP administration. Also in rats, however, high doses of MPP+ were measured in the striatum of MPTP-alone treated rats and DDC delayed the MPP+ elimination from the striatum. When MPTP alone or DDC + MPTP was administered to rats unilaterally lesioned with 6-hydroxy dopamine (6-OH-DA), the levels of MPP+ measured in the intact striatum were significantly higher than those found in the 6-OH-DA-lesioned striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to monkeys: behavioural, morphological and biochemical correlates.

The behavioural, biochemical and morphological effects of a chronic administration of low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in the common marmoset. Monkeys received the toxin (1 mg/kg i.p.) twice a week for four months. Group A monkeys were studied one week after the last injection of MPTP; group B monkeys were studied eight months after the last toxic injection. The monkey behaviour was observed throughout the experiment; the biochemical and morphological correlates were studied post mortem in the neostriatum and in the substantia nigra, respectively. Data collected from MPTP-treated marmosets were compared to those obtained from sham-injected control monkeys. The results can be summarized as follows. (1) In all MPTP-treated marmosets a progressive Parkinsonism occurred. In group B monkeys, a gradual behavioural recovery was observed after MPTP was discontinued. (2) Biochemical analysis of group A marmosets showed a depletion of dopamine, of 3,4-hydroxyphenylacetic acid and of homovanillic acid, and no variations in dopamine turnover in the neostriatum of MPTP-treated marmosets. In group B, biochemical analysis showed no differences between controls and MPTP-treated animals. (3) Morphological analysis showed that the density of midbrain dopaminergic neurons located in the substantia nigra was unchanged in group A monkeys, but was reduced by 6.8% in MPTP-treated monkeys of group B. The measurement of cross-sectional area showed that midbrain dopaminergic neurons were swollen in MPTP-treated monkeys of group A, with a 11.0% increase of cell size as compared to controls. In group A the nuclei were also swollen, being 304.8% larger in MPTP-treated monkeys, with a nucleus-to-cytoplasm ratio of 65.9% (as compared to 34.0% of controls). In group B monkeys cell size was increased by 18.4% in MPTP-treated marmosets, but the nuclei were of comparable size. The present data show that a chronic administration of low doses of MPTP brings about biochemical and morphological abnormalities. The first occur acutely in terminals and are reverted early after discontinuance of exposure to the toxin; the latter occur in dopaminergic perikarya, last longer than biochemical abnormalities and, at variance with them, increase in severity after MPTP is discontinued. Morphological abnormalities include early events, such as a transient swelling of nuclei or a long-lasting swelling of neurons, and late events, such as a decrease in the number of tyrosine hydroxylase-positive perikarya.(ABSTRACT TRUNCATED AT 400 WORDS)