Physiology and Pharmacology
Volume:21 Issue: 4, Dec 2017

Recent reports have shown that rare fluctuations in cardiac cycles are ‘forgotten’ quickly in healthy individuals and it is possible to quantify the “memory length” of a physiological time-series using an inverse statistical approach.
In the present study, we assessed the effect of aging on memory length in cardiac rhythm.
There was a longer memory length in cardiac time-series of elderly subjects in comparison with younger adults for both decelerating and accelerating rare fluctuations in cardiac rhythm.
The increased memory length of the cardiac time-series in elderly subjects may indicate reduced controllability of cardiovascular regulatory system.

Unilateral ureteral obstruction (UUO) is a clinical scenario that leads to obstructive nephropathy. UUO alters the expression of many mediators in the ipsilateral kidney. Renin-angiotensin system (RAS) is involved in UUO. Angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7) as the main arms of RAS influence kidney function which may alter by UUO. Ang II via Ang II receptor subtypes I (AT1R) reduces renal blood flow and glomerular filtration rate and induces oxidative stress, apoptosis as well as inflammation in renal tissue and contributes to renal fibrosis in UUO model. Also, Ang 1-7 receptor (MasR) and Ang II receptor subtype II (AT2R) may have a protective effect against UUO-induced renal injury. In addition, there is crosstalk among RAS with the main vasodilator factors (prostaglandins E2 and I2, bradykinin, atrial natriuretic factor, nitric oxide and adenosine) and the main vasoconstrictor factors (endothelin and vasopressin) in the ipsilateral kidney with UUO. In this review, the roles of the RAS on renal function and its interactions with the other factors in the kidney with UUO were discussed.

Ferulic acid, a phenolic phytochemical with neuroprotective, anti-inflammatory, and antioxidant properties, has shown promising antidepressant-like effects in behavioral studies; however, its mechanism(s) of action have not been fully understood. Based on the contribution of nerve growth factor (NGF) and endocannabinoid signaling (eCBs) to the emotional or antidepressant activity and their interaction, we aimed to evaluate whether ferulic acid affects NGF or eCB contents in the brain regions involved in the modulation of emotions.
Following single and four-week once-daily intraperitoneal injections of ferulic acid (50, 100, 130 and 150 mg/kg), amitriptyline (2.5, 5, 8 and 10 mg/kg) or lorazepam (2, 5, 8 and 10 mg/kg) into male Wistar rats, NGF and eCB levels were quantified by Bio-Rad protein assay and isotope-dilution liquid chromatography/mass spectrometry. In the case of significant alteration of brain NGF or eCB content, the effects of pre-treatment with cannabinoid CB1 or CB2 receptor antagonist (AM251 or SR144528) were investigated.
Four-week treatment with the highest doses of ferulic acid or amitriptyline led to a significant and sustained enhancement of eCB and NGF contents in brain region-specific fashion. Neither acute nor four-week treatment with lorazepam affected NGF or eCB levels. Pre-treatment with AM251 (3 mg/kg), but not SR144528, prevented the elevation of NGF levels. AM251 showed no effect by itself.
Ferulic acid similar to the conventional antidepressant, amitriptyline, affects brain eCB and NGF signaling. CB1 receptors mediate the production of brain NGF.

A relationship between epileptic seizures and brain tissue oxidative damage has been suggested. Ocimum basilicum (O. basilicum) has been shown to have beneficial effects including hypnotic and protective against tissue oxidative damage. The present study was designed to evaluate the effects of O. basilicum hydro-alcoholic extract on oxidative damage of brain tissue following seizures induced by pentylenetetrazole (PTZ) in mice.
The animals were grouped and treated as follows: 1- control group which received saline; 2- PTZ group (90 mg/kg, ip); 3 to 5- three groups which received 25, 50 or 100 mg/kg of a hydro-ethanolic extract of O. basilicum before PTZ. First minimal clonic seizure (MCS) and the first generalized tonic-clonic seizure (GTCS) latencies were analyzed. The brains of the animals were then collected and stored to use for biochemical evaluation.
The plant extract in 50 and 100 mg/kg doses, significantly postponed the MCS and GTCS seizures onsets (P The current study revealed that hydro-ethanolic extract of O. basilicum possesses significant antioxidant and anticonvulsant activities.

Schizophrenia is a chronic mental illness, whose aetiology is still unclear; therefore, information about differences in serum protein patterns may improve the understanding of the pathophysiology of schizophrenia. The goal of this study was to use the proteomic approach to identify altered protein levels in the serum samples from patients with schizophrenia.
Blood was collected from 10 patients with paranoid schizophrenia and 10 healthy volunteers matched by sex and age. Serum proteins were isolated by 2D gel electrophoresis. Proteins with altered levels were identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry.
We uncovered major changes in the expression of such proteins as apolipoproteins of classes A4 and C3, transthyretin (TTR) and serum amyloid A1. An increase in expression was found only for apolipoprotein A4, whereas the expression of apolipoprotein C3, TTR and serum amyloid A1 was decreased. The observed differences in the expression of serum proteins (TTR and serum amyloid) are in good agreement with the results obtained by other research groups during analyses of cerebrospinal fluid or post-mortem brain tissues by other methods.
Such alterations of the expression of these proteins may indicate problems with regulation, for example, in the synthesis. On the other hand, the altered protein expression may simply reflect the pathophysiological status of patients, where these proteins could be candidates for biomarkers. Further research is needed to confirm the significance of the altered levels of these proteins in the pathogenesis of schizophrenia and to determine their suitability as biomarkers of schizophrenia.

In this study, we evaluated the antidiabetic and antidiabetogenic effect of saffron against diabetes induced by artificial dye tartrazine on normal male rats.
Dried saffron was macerated for 12 hours in distilled water before usage and crude extract was used to treat male rats. Rats were divided into 5 groups consisted of 6 rats and treatment was performed daily and orally. Group-1 treated with distilled water, group-2 with tartrazine 10mg/kg followed by saffron 120mg/kg until the last day of treatment, group-3 administered with tartrazine, group-4 treated with saffron for 60 days and administered with tartrazine, group-5 with saffron for 105 days. Levels of blood glucose and body weight have been evaluated every 10 days and clinical demonstrations and metabolic parameters were evaluated at the end of the experiment.
Levels of blood glucose and body weight have been evaluated every 10 days and clinical demonstrations and metabolic parameters were evaluated at the end of the experiment. Results showed that treatment with tartrazine and saffron did not affect body weights, metabolic parameters but changed the blood glucose levels after 105 days of administration. The levels of glucose and creatinine were significantly increased in group-2 and group-3 compared to control group (P0.05). Treatment with saffron decreases creatinine level.
The outcomes suggest that saffron has curative (antidiabetic) and protective (antidiabetogenic) effect against diabetes induced by tartrazine via reducing blood glucose level and creatinine. Therefore, it should be considered in future therapeutic researches.

Mutations in the delta sarcoglycan gene (d-SG) cause limb-girdle muscular dystrophy type 2F with structural and functional alterations in cardiac, smooth and skeletal muscle. The objective of the present study was to improve information about changes in vascular reactivity of the thoracic aorta and the coronary artery in the perfused heart of the d-SG-null mutant mouse model.
Female knockout (KO) and wild-type (WT) mice (5 months old) with and without nitric oxid and prostanoids antagonist were used. Curves doses response to phenylephrine, angiotensin II and acetylcholine were constructed.
The results shows an increment in the contractile response to angiotensin II in the aorta and the isolated heart from the KO mice, and it seems due to a major participation of prostanoids. On the other hand the relaxant effect of acetylcholine is less in the KO than in the WT mice.
Changes in vascular reactivity in KO mice seems due to the participation of prostanoids instead of nitric oxide.

Treatment of lung diseases is one of the major healthcare challenges. Ferulic acid (FA), a phenolic compound with well-established antioxidant and anti-inflammatory properties, has shown promising therapeutic potential against the pulmonary disorders; however, low bioavailability may negatively affect its efficiency. This, prompted us to incorporate FA into the nanostructured lipid carriers (FA-NLCs) and evaluate the toxicity of this nanoformulation in human lung adenocarcinoma cell line (A549) and its suitability for pulmonary drug delivery.
FA-NLCs were prepared by high-pressure homogenization followed by assessment of the physicochemical properties of nanoparticles, in vitro release profile, aerosol characteristics, in vitro cytotoxicity, pharmacokinetic parameters and lung deposition of the nanoparticles after nebulization in Balb/c mice.
Formation of FA-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. FA-NLCs exhibited toxic effects on A549 cells for longer time periods as compared to FA solution. Following the aerosolization, suitable aerodynamic properties were obtained and FA-NLCs formulation provided significantly increased residence time and slower lung clearance for FA. Further confocal microscopy visualization confirmed the lung deposition of nanoparticles. Encapsulation of FA into the NLCs resulted in the improved pharmacokinetic parameters in plasma or lung tissue samples.
Application of the aerosolized FA-NLCs formulation which improves the pulmonary bioavailability of FA might result in the increased efficiency and reduced dosing frequency of this phytochemical. In this respect, development of inhalable nano-based drug delivery systems appears as a promising therapeutic approach against the lung disorders.

The aim was to investigate the protective effect of the Syzygium aromaticum extract on damaged tissues and the oxidative stress after testicular torsion.
Rats were randomly divided into a control group subjected to a sham procedure and three treatment groups comprising testicular torsion followed by detorsion (TD), testicular torsion detorsion followed by the treatment with an extract of Syzygium aromaticum (TDSA) and treatment done by extract of Syzygium aromaticum alone. Testicular torsion was induced by 720 degrees of counterclockwise rotation of the left testis for 4h. After the duration of the induction of the torsion, detorsion was done. The animals were given daily oral administrations of just Syzygium aromaticum (4 mg/kg) for seven days. The measurement of the oxidative stress and testosterone levels, as well as assessments of histomorphometry were conducted seven days after detorsion.
The Johnsen score, along with the thickness of the epithelium and diameter of the seminiferous tubules, significantly increased in the testicular torsion group after receiving treatment with the extract of Syzygium aromaticum as compared to TD group. The levels of testosterone and glutathione peroxidase activity also increased significantly in the TDSA compared to TD group. The MDA levels decreased in TDSA compared to TD group.
The findings of the current study suggested that Syzygium aromaticum might have provided a protective effect against testicular torsion detorsion injury.