Petra Kieslinger

Increased matrix metalloproteinase activity is associated with migraine and migraine-related metabolic dysfunctions

Objective:  Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are discussed to be involved in the pathophysiology of migraine. Moreover, MMPs may also be involved in migraine‐related metabolic alterations like an atherogenic lipid profile and hyperinsulinemia. The aim of this study was to investigate the impact of MMPs and TIMPs on migraine with and without aura and related metabolic dysfunctions.

GLP-2 and leptin are associated with hyperinsulinemia in non-obese female migraineurs

Objective: Impaired insulin metabolism has been implicated in migraine. However, to date only some putative effects, especially regarding the involvement of adipocytokines and glucagon-like peptides (GLPs), have been described. The aim of the present study was to investigate adipocytokines and GLPs in non-obese female migraineurs. Methods: Various parameters of the insulin metabolism and body measurements were determined in 84 non-obese female subjects. Results: We found highly significantly increased insulin levels with an odds ratio of 10.62 for migraine. Leptin and GLP-2 levels were also increased and correlated with insulin. Logistic regression analysis of leptin and GLP-2 revealed odds ratios of 3.79 and 4.26 for migraine, respectively, when comparing the lowest with the highest quartile of the test variable in the complete study cohort. Discussion: We show that non-obese female migraineurs suffer from hyperinsulinemia, which is associated with elevated leptin and GLP-2 levels. Increased leptin and GLP-2 are risk factors for migraine. Our data suggest that migraine is associated with a higher risk for insulin resistance and its clinical consequences.

Treatment with the nitric oxide donor SNP increases triiodothyronine levels in hyper- and hypothyroid Sprague-Dawley rats.

Nitric oxide pathway might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of nitric oxide (NO) on hypothyroid and hyperthyroid Sprague-Dawley rats under controlled diet. Furthermore, the effects of the nitric oxide donor sodium nitroprusside (SNP) on thyroid dysfunctions were also assessed. Sprague-Dawley rats (n=107) were subdivided into normal diet and high-fat diet (HFD) groups and grouped into controls, hypothyroid, hyperthyroid, and SNP treated groups. Hypothyroidism was induced through propylthiouracil, whereas hyperthyroidism by triiodothyronine (T3). After 12 weeks of T3 treatment, serum nitric oxides (NOX), endogenous asymmetric dimethylarginine (ADMA), body weight and food intake were analyzed. Hypothyroid rats showed decreased serum T3 levels, hyperthyroid rats increased T3 compared to controls. Diet had no impact on T3. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight. Serum NOX was significantly reduced in normal diet hypothyroid rats. SNP administration compensated the decrease and markedly increased T3. NO synthase inhibitor ADMA levels were significantly higher in the HFD control group than in the normal diet controls. ADMA was declined in both hypothyroid groups and increased in normal diet hyperthyroid rats. An association of thyroid dysfunctions with reduced bioavailability of NO and alterations of ADMA levels could be established. Treatment with the NO donor SNP resulted in an increase of serum T3 levels. These results demonstrate that the NO pathway is implicated in thyroid dysfunctions, which may be of clinical relevance.

Circulating leptin and NF‐κB activation in peripheral blood mononuclear cells across the menstrual cycle

Using the menstrual cycle as a model, this study focused on longitudinal changes and associations within a physiological network known to play a role in female fertility, including, as biologically active nodes, NF-κB, leptin and adiponectin, β-carotene, adipose tissue, and progesterone. In 28 women, leptin, adiponectin, β-carotene, and progesterone concentrations, NF-κB p65 and p50 activation in peripheral blood mononuclear cells (known to possess estrogen, progesterone and leptin receptors), total body fat (TBF) and subcutaneous adipose tissue (SAT) mass were determined at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase. Leptin and adiponectin concentrations were higher, while NF-κB p65 activation was lower at T3 compared with T1. NF-κB p65 activation was inversely related to leptin concentrations at T1, T3, and T4. β-Carotene was inversely related to leptin (T1,T2,T4) and SAT (T1,T3,T4). NF-κB p50 activation was inversely related to TBF (T4) and SAT (T3,T4), and leptin was positively related to TBF and SAT (T1-T4). Progesterone was inversely related to leptin (T2,T3), adiponectin (T3), TBF (T3,T4), and SAT (T2,T3,T4). By providing evidence of luteal phase-specific reduced NF-κB p65 activation in women under physiological conditions, this study bridges the gap between existing evidence of a Th1-Th2 immune response shift induced by reduced NF-κB p65 activation and a Th1-Th2 shift previously observed at luteal phase. For the first time, inverse regressions suggest inhibitory effects of leptin on NF-κB p65 activation at luteal phase, along with inhibitory effects of leptin as well as adiponectin on progesterone production in corpus luteum.

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

Decreased viability and proliferation of CHANG conjunctival epithelial cells after contact with ultraviolet light-irradiated pollen

Abstract Context: Contact with pollen is the major reason for the development of allergic symptoms on the ocular surface leading to a significant increase of allergic diseases worldwide. Environmental changes such as increased ultraviolet (UV) radiation and air pollution are discussed as contributory causes for this increase. Objective: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells. Materials and methods: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system. Results: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen. Discussion and conclusions: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells.

Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet.

Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased—and hyperthyroid animals significantly decreased—ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.