Gender-related differences in systemic sclerosis

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease which is characterised by autoimmunity, widespread tissue fibrosis of the skin and internal organs, and vasculopathic alterations. SSc is more common in women but has a more severe expression of disease including internal organ-based complications and higher mortality in men. The extant literature shows that although important pathophysiological sex differences are present in SSc, behavioural differences (e.g. higher smoking rates in men) and occupational exposures may contribute to poorer outcomes in men with SSc. The higher death male death rate in the general population and greater prevalence of lung fibrosis are likely the key factors responsible for excess mortality found in men. Other important factors include (but are not limited to) a greater prevalence of the disease subset, delayed time to diagnosis, and higher disease activity in early disease in men. SSc carries a significant burden of disease-related morbidity; however, no qualitative studies to date have focussed on gender differences in SSc. The purpose of this review is to provide a comprehensive overview of gender differences in SSc including (but not limited to) epidemiology, pathophysiology, clinical expression of disease, mortality, SSc in transgender individuals, and psychosocial aspects of disease.     

Gender-related dissociations of categorical fluency in normal subjects and in subjects with Alzheimer's disease

Semantic fluency tasks, with the categories of birds and furniture as stimuli, were administered to normal subjects and patients with Alzheimer's disease (AD). Normal subjects showed a gender-related double dissociation consistent with the literature data because men were more fluent with the birds category and women with the furniture category. Also, patients with AD showed a Gender x Category interaction, but the double dissociation between birds and furniture was not present because of a prevalent impairment of the living category birds that was irrespective of gender. This pattern of impairment in patients with AD was independent from the disease stage. The authors conclude that (a) gender-related categorical effects cannot be considered as inborn, sex-related cognitive differences but as familiarity effects and (b) both lesion-related and familiarity-related factors must be taken into account to explain category-specific effects of patients with brain damage and patients with AD.     

Gender-related sleep differences in neonates in thermoneutral and cool environments

Although thermoregulation and sleep exhibit gender differences in adults, the question is still debated in neonates. The aim of this study was to examine the relationship between gender-related sleep differences and cool defence mechanisms in neonates. Sleep and thermoregulation were recorded in healthy preterm neonates (21 boys and 17 girls, 37 +/- 2 weeks post-conceptional age) exposed to thermoneutral and cool conditions. Sleep was analysed for continuity and structure. Although the cool exposure did not strongly impair body homeothermia, sleep was altered but without any significant gender difference. However, when data recorded under each of the thermal conditions were pooled, some gender differences emerged: boys slept less, with more wakefulness after sleep onset, more active sleep and less quiet sleep than girls. In contrast to sleep architecture, most of the sleep continuity parameters exhibited greater variability in boys than in girls. This variability may bias the statistical analyses and probably explains the varying conclusions reported in the literature regarding gender-specific sleep-related differences.     

Gender-related differences in the rates of age associated thymic atrophy

Age associated thymic atrophy has been shown to be linked to problems with rearrangement of the beta chain of the T cell receptor (TCR) in male mice during the early phases of the intrathymic T cell developmental pathway. In this study, thymic atrophy in female mice was found to occur at a different rate than in male mice. At 9 months of age there was a significantly greater number of cells in the thymus of female mice compared with male mice, with the major difference found in the CD4+CD8+ populations. The thymii of female mice at 9 months of age contained double the number of these cells compared with male mice. Analysis of the CD4+CD8+ cells at 9 months of age demonstrated increased numbers of cells expressing higher levels of CD3 in females compared with males indicating that in females more of these cells were producing successful alphabetaTCR pairings. In F5 transgenic mice comparison of the CD4+CD8+ population revealed no significant difference in their absolute numbers at 9 months of age. These results indicate that the gender differences at this time point were due to fewer permitted divisions prior to the expression of a selectable TCR alpha chain within the CD4+CD8+ populations in male compared with female mice. This gender difference was not due to the action of testosterone and unlikely to be due to differences in the level of oestrogen. The potential mechanisms of this difference may be related to a regulatory feedback of peripheral T cells on the developing thymocyte populations. Such age related changes in the numbers of cells within distinct thymic subpopulations leads to the possibility that the potential repertoire in females is greater than in males later in life.     

Gender-related and age-related urinalysis of healthy subjects by NMR-based metabonomics

NMR-based metabonomic analysis is a well-established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter-individual variability in the metabolic urinary profile of a healthy Greek population, not subjected to strict dietary limitations, by NMR-based metabonomics. The overall metabonomic urinalysis showed a homogeneous distribution among the population. The metabolic profile was examined in relation to gender and age, and reference intervals of major metabolites were determined. Multivariate data analysis led to the construction of two robust models that were able to predict the class membership of the subjects studied according to their gender and age. The most influential low molecular weight metabolites responsible for the differences in gender groups were citrate, creatinine, trimethylamine N-oxide, glycine, creatine and taurine, and for the differences in age groups they were citrate, creatinine, trimethylamine N-oxide and an unidentified metabolite (delta 3.78).     

Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics

Summary ¶A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.Received February 3, 2003; accepted March 11, 2003 Published online June 26, 2003     

Molecular properties of each subcomponent in Clostridium botulinum type B haemagglutinin complex

The role of each subcomponent of Clostridium botulinum serotype B haemagglutinin (HA), which is one component of 16S toxin, and consists of four subcomponents (HA1, 2, 3a, and 3b), was investigated. In order to identify the subcomponent contributing to the stability of a neurotoxin in the gastro-intestinal tract, each recombinant HA (rHA) subcomponent was incubated with gastro-intestinal proteases. Although rHA1 and rHA3 were stable to these proteases except for specific cleavage, rHA2 was not. Anti-free whole HA serum reacted with neither rHA2 nor HA2 in 16S toxin on both Western blot and ELISA, while anti-rHA2 serum reacted with both rHA2 and HA2 in 16S toxin on Western blots, although it did not react with 16S toxin in ELISA. Binding or haemagglutination activity against erythrocytes was found in rHA1 and rHA3, but not in rHA2. In addition, only HA1 bound to the intestinal section. These results indicate that the HA (and 16S toxin) complex is assembled in the way that HA1 and HA3 (HA3a plus HA3b) encase HA2, followed by modification with trypsin-like bacterial protease, leading to the conclusion that HA1 and HA3 act as protective factors for the neurotoxin and as attachment factors to host cells.     

Inter-individual differences in breathing pattern at high levels of incremental cycling exercise in healthy subjects

Interindividual differences in the rate of changes in tidal volume (V_T) and respiratory frequency (f_R) were examined during a maximal incremental cycling exercise. The gain of the inspiratory off-switch reflex was inferred from the V_T vs. inspiratory duration (T_i) relationship. Some subjects also executed a static handgrip exercise, used as a “non-dynamic” exercise trial to study patterning of breathing.     

Gender-related differences in symptoms of patients with suspected breathing disorders in sleep: a clinical population study using the sleep disorders questionnaire

BACKGROUND: Gender-related differences in the symptom profile of patients with suspected sleep disordered breathing (SDB) may be one explanation of the clinical underrecognition of SDB in women. STUDY OBJECTIVES: The aim of this study was to prospectively assess gender-related differences in presenting symptoms in a clinical sample of patients with suspected sleep disordered breathing. DESIGN: Administration of the Sleep Disorders Questionnaire prior to clinical and polysomnographic evaluation. Responses obtained from the questionnaire were used to construct 4 independent symptom scales: sleep apnea (SA), periodic limb movement syndrome (PLM), psychiatric sleep disorder (PSY), and narcolepsy (NAR). Analyses of variance were used to examine the effect of gender, AHI, and age on the symptom scales. Associations between gender and each diagnostic scale of the questionnaire were determined by multiple analyses of covariance. SETTING: Tertiary pulmonary referral center. PARTICIPANTS: 2739 men and 782 women with suspected SDB. All patients who were referred to the sleep laboratory underwent full-night polysomnography, irrespective of the likelihood of SDB. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Overall, men scored significantly higher on items related to worsening of snoring/breathing with alcohol (P < 0.001) and smoking history (P < 0.01) than women. Complaints such as witnessed apneas (P < 0.001) and worsening of snoring in supine position (P < 0.05), however, were more frequently reported by men with an apnea-hypopnea index (AHI) < 5/hr, compared with AHI-matched women. There were no significant differences in these items in patients with an AHI > 15/hr. In contrast, women complained significantly more often of insomnia, restless legs, depression, nightmares, palpitations at night, and hallucinations than men. As a result, women had significantly higher scores on the PLM, PSY, and NAR scales of the Sleep Disorders Questionnaire (P < 0.001, for all). After adjustments for age, body mass index, AHI, arousal index, oxygen saturation data, and smoking history, by means of multiple analyses of covariances, gender differences remained significant (P < 0.001, for all scales). CONCLUSIONS: We observed significant gender-related differences in presenting symptoms of patients with sleep disordered breathing at a tertiary level. These differences should be taken into consideration in clinical evaluation of women with suspected sleep disordered breathing.     

Gender-related differences in the regulatory influence of thyroid hormone on the expression of myosin isoforms in young and old rats

The effects of 4 weeks of thyroid hormone (3,5,3′-triiodothyronine, T3) treatment on the expression of myosin heavy chain (MyHC) isoforms were examined in young (3–6 months) and old (20–24 months) female rats, and compared with those in age-matched male rats (Larsson et al. 1995). In control rats, ageing was associated with a type IIA to I MyHC isoform switching in the slow-twitch soleus and a type IIB to IIX MyHC isoform switching in the fast-twitch extensor digitorum longus muscle (EDL). Gender- and muscle-specific differences were observed in the regulation of MyHC isoforms by T3. In the soleus, dramatic downregulation of the type I and upregulation of the type IIA MyHC isoform were observed in both females and males, but upregulation of the IIX MyHC isoform was observed only in male rats. In EDL, T3 treatment had no significant influence on the MyHC isoform composition in the males irrespective of the age of the animal. In the females, on the other hand, T3 treatment resulted in a significant MyHC transformation from IIA to IIB, probably via IIX myosin, in spite of the fact that type IIA mRNA has been reported to be downregulated in both females and males. It is concluded that the regulation of MyHC isoforms by thyroid hormone differs between females and males, presumably as a result of a gender-related difference in the translational or post-translational regulation of MyHC synthesis.     

Matrix metalloproteinases in subjects with type 1 diabetes

Background  

Nephropathy is serious complication of diabetes. We have previously shown that level of the proteoglycan syndecan-1 in blood is associated with ultrastructural kidney changes in young persons with type 1 diabetes. Dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) may contribute to the development of nephropathy. The aim of this study was to investigate if the levels of MMPs in blood samples are potential markers of early nephropathy in type 1 diabetes.     

Forearm vasoreactivity in type 1diabetic subjects.

This study compared forearm vasoreactivity in 15 Type I diabetic subjects with 15 healthy controls. The groups were matched for age, exercise capacity, and the absence of other cardiovascular risk factors. Vasoreactivity was measured using strain gauge plethysmography, at rest, after arterial occlusion (OCC), and following OCC coupled with handgrip exercise (ROCC). Forearm blood flows were significantly elevated between conditions 2.58 +/- 0.37ml/100mltissue at rest to 26.80 +/- 6.56 after OCC and 32.80 +/- 8.26ml/100mltissue following ROCC in Type I diabetic subjects. There were no differences in forearm blood flow between groups for any of the conditions. These data indicate the degree of forearm blood flow is directly related to the intensity of the vasodilatory stimulus. However, our study did not reveal evidence of impaired vasodilatory capacity in Type I diabetic subjects compared to controls in the absence of other risk factors.     

Fibronectin interacts with Clq, a subcomponent of the first component of complement

Human Clq, a subcomponent of the first component of complement interacts with human fibronectin. Using ELISA methodology fixation of Clq to solid phase fibronectin, as well as fibronectin to solid phase Clq has been demonstrated. Cl in its native macromolecular form displays little reactivity for fibronectin, nor does Cl reconstituted from Clq, Clr and Cls in the presence of Ca2+ ions. Heating of Clq above its thermal transition temperature (51 degrees C) induces an increased binding capacity for fibronectin. On the other hand, a mixture of the dissociated A, B and C chains of Clq is less active than native Clq. The binding of fibronectin appears to be mediated by the A chain. Studies with Clq deprived of its globular parts by peptic digestion indicate that the collagen-like regions of Clq are involved in fibronectin binding. In contrast, collagenase treatment of Clq abrogates its fibronectin binding capacity.     

Sex differences in cue perception in a visual scene: investigation of cue type

Sex differences in spatial navigation indicate that women may focus on positional, landmark cues whereas men favor Euclidean, directional cues. Some studies have investigated sex differences in proximal and distal cue use; however, sex differences in gradient (i.e., graded features) and pinpoint (i.e., single, defined) cue perception remain unexamined. In the current experiments, paired photographs were presented in which the 2nd photograph showed the same scene with cues removed (Experiment 1) or isolated (Experiment 2) from the 1st photograph. In Experiment 1, women showed less disruption of task performance than men showed following cue removal but were slowest after proximal pinpoint cue removal. Male performance was slowed by distal gradient and proximal pinpoint cue removal. In Experiment 2, women were faster than men at identifying isolated proximal and distal pinpoint cues and were more accurate at identifying isolated distal gradient and distal pinpoint cues. Better pinpoint cue perception and memory in women indicates one possible mechanism underlying female preference for landmark-based navigation strategies. Findings also show that whereas men may preferentially rely on distal gradient cues they are not better at perceiving those cues than are women.     

Secondary tactile hypoesthesia: a novel type of pain-induced somatosensory plasticity in human subjects

Quantitative sensory testing revealed that pain induced by intracutaneous capsaicin injection elicited secondary hyperalgesia coexisting with secondary tactile hypoesthesia. Mapping the areas of altered mechanical sensations adjacent to the capsaicin injection disclosed that the area of secondary hyperalgesia was always nested in a larger area of secondary hypoesthesia easily detected as numbness by most subjects. Psychometric functions revealed a twofold rightward shift of tactile detection (hypoesthesia), which coexisted with a more than fourfold leftward shift of pricking pain detection (hyperalgesia) in the same skin area. As a mechanism we propose a functional switch at the spinal level based on C-fibre-induced primary afferent depolarisation resulting in presynaptic inhibition of low threshold mechanoreceptor input and an ensuing loss of tactile sensitivity.     

Cardiac output in paraplegic subjects at high exercise intensities

Summary The purpose of this investigation was to compare cardiac output ( _c ) in paraplegic subjects (P) with wheelchair-confined control subjects (C) at high intensities of arm exercise. At low and moderate exercise intensity _c was the same at a given oxygen uptake ( O₂) in P and C. A group of 11 athletic male P with complete spinal-cord lesions between T6 and T12 and a group of 5 well-matched athletic male C performed maximal arm-cranking exercise and submaximal exercise at 50%, 70% and 80% of each individual's maximal power output (W_max) . Maximal O₂ ( O_2max) was significantly lower, O_2max per kilogram body mass was equal and maximal heart rate (f _c) was significantly higher in P compared to C. At O₂ of 1.3, 1.5 and 1.7 1-min^–1, and for P 65%–90% of the O_2max, _c was not significantly different between the groups, although, _c in P was achieved with a significantly lower stroke volume (SV) and a significantly higherf _c. Although the SV was lower in P, it followed the same pattern as SV in C during incremental exercise, i.e. an increase in SV until about 45%W _max and thereafter a stable SV. The similar _c at a given O₂ in both groups indicated that, even at high exercise intensities, circulation in P can be considered isokinetic with a complete compensation byf _c for a lower SV.