sima sadrai

In Traditional Persian Medicine (TPM) saffron is used as an accompaniment agent “Mobadreq” in poly herbal formulations. According to TPM texts, “Mobadreq” is a substance (or drug) which facilitates access of drugs or food to the whole body or specific organs. This study investigated the effect of oral co-administration of Crocus sativus L. (saffron) on the absorption and some pharmacokinetic parameters of acetaminophen in rats. Two groups of Rats (n=6) were treated by 1: acetaminophen 10 mg/kg along with Crocus sativus 4 mg/kg (test group) and 2: 10 mg/kg acetaminophen (control). The plasma concentrations of acetaminophen after oral administration (at 0, 5, 10, 15, 20, 40, 60, 90, and 120 min) were monitored by an HPLC-UV method. Results indicated that the plasma concentration of acetaminophen in the test group was reached to the maximum concentration (Cmax) faster than control group. As a result, at 5 to 40 minutes after drug gavage, the concentration of acetaminophen in both groups was significantly different.  It was also found that co-administration of acetaminophen and saffron significantly increased acetaminophen’s area under concentration curve (AUC0-60) in compare to the acetaminophen alone (p<0.025). These results suggested that saffron could increase absorption rate of acetaminophen. Consequently, saffron can be considered and introduced as an enhancer of absorption rate and efficacy of acetaminophen and other drugs at least by oral route although the drug interactions with this herb should be considered.

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.

Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI).

This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures. For all the patients, phenytoin serum concentration was determined in three scheduled time points. Phenytoin serum concentration and pharmacokinetic parameters were compared between patients with TBI and cerebrovascular accident (CVA).

The Vmax and Km were significantly higher in head trauma (HT) patients than the CVA group. The phenytoin concentration (Cp ) and the Cp /dose ratio were significantly higher in the CVA group patients during the first sampling (P < 0.05). The Acute Physiology and Chronic Health Evaluation П (APACHE П) score was significantly lower than the baseline at the end of the study in each group of patients (P < 0.05). In addition, no significant correlation was observed between Vmax, Km, Cp , Cp /dose ratio, and APACHE II scores at the time of sampling.

Due to significant differences in phenytoin plasma concentration and pharmacokinetic parameters between HT and CVA patients, close attention must be paid to the pharmacokinetic behavior of phenytoin in the efforts to improve the patient’s outcome after a severe HT.

Eryngium caeruleum M.Bieb. (Syn. Eryngium caucasicum Trautv.)belongs to Apiaceae family. It is found abundantly in northern provinces of Iran as an edible plant. Hundreds of years ago, Eryngium genus was known as a medicinal herb in Persian medicine books which was named “Qaracaane” and the plant’s roots were used in traditional medicine. The aim of this study was to evaluate the nutritional parameters in roots, spring and autumn leaves of E. caucasicum for the first time.

The parameters including proximate composition (protein, carbohydrate, fat, fiber, ash, moisture and calorie) were measured by the standard methods of the AOAC, mineral contents (iron, zinc, copper and manganese) were measured by atomic absorption and amino acid contents was measured by RP-HPLC.

Regarding the results, it was found that the autumn leaves showed the highest amount of fiber, protein, moisture, zinc, copper and manganese. Also, spring leaves contained the highest levels of calorie, while the roots showed much more ash, carbohydrate and iron content. In terms of amino acids contents, threonine was the dominant among the rest of essential amino acids in all investigated parts of E. caeruleum. The results showed that both the aerial parts and the roots of Eryngium caeruleum could be good sources of nutritional ingredients.

According to the obtained results it can be concluded that E. caeruleum has the capacity for prospective production of new natural medicinal supplements in order to improve body health and prevent or treat diseases.

Traditional medicine could provide a hopeful area of research to mitigate the suffering of patients. “Qust” is one of the medicinal plants that are mentioned in Persian Medicine (PM) for treatment of neurological diseases. There is diversity within the scientific name of “Qust” in different references. Some have introduced Saussurea costus (Falc.) Lipsch. (Asteraceae), while others have presented Costus speciosus (J. Koenig) Sm. (Costaceae) as “Qust”. Since “Qust” is not endemic in Iran, there is difficulty to access to the whole plant for its identification. Hence, this study has aimed to identify available bitter “Qust” which is composed of roots of the plant in the Iranian market.

Macroscopic characters and microscopic properties of powders and transverse sections of specimens with essential oil analysis of the Indian and one of the Iran herbal market samples using chromatography-mass spectrometry (GC-MS) were investigated for identification of bitter “Qust”.

Microscopic evaluation showed presence of secretory cavities and their specific size, narrow radial rows of conducting tissue alternating with broad medullary rays in the secondary phloem and xylem, presence of inulin, absence of starch and calcium oxalate crystals in the bitter “Qust” particles. Further, positive response was observed to S. costus identifying test. In the analysis of essential oils, active components of S. costus, such as dehydrocostus lactone, were identified in the examined essential oils.

According to the results, it could be concluded that bitter “Qust” in Iran herbal market most probably is S. costus.

L-tryptophan is used widespread in the pharmaceutical industry. The majority of L-Trp production depends on microbial processes that produce L-tryptophan from indole and L-serine. These processes are very costly due to the costs of precursors, especially L-serine. Use of inexpensive substitutions as the L-serine source of Ltryptophan production enables us to reach a cost-effective process. In this paper, effect of Triton X-100 on L-Trp production and the ability to use Iranian cane molasses as inexpensive L-serine source was investigated.
Escherichia coli (E. coli) ATCC 11303 cells were grown in 10-L fermenter containing minimal medium supplemented with beet molasses as an inexpensive carbon source and indole as tryptophan synthase inducer. Whole cells of stationary phase were used as biocatalyst for L-Trp production. Triton X-100 addition to the production medium as indole reservoir was investigated. Then, cane molasses was used as LSer source in L-Trp production medium. Amount of L-Tryptophan and theoretical yield of L-Trp production was determined by HPLC and by a colorimetrically method on the basis of remaining indole assay, respectively.
As a result, triton X-100 increased L-Trp production three times. Also, the result showed that 0.68 mM L-Tryptophan was produced in the presence of cane molasses at 37 C for 8 hr .
This result showed that cane molasses of Qazvin sugar factory includes significant amounts of L-Ser that makes it a suitable substitution for L-Ser in L-Trp production. Therefore, it has the potential to be used for cost-effective L-Trp production in industrial scale.

‘Palpitation’ is one of the most common complaints in patients referring to cardiologists. In modern medicine era, these patients suffer from much distress and some cases are known to be difficult to treat. Although the clinician’s first duty is obviously to search for an organic basis for this symptom, the diagnostic evaluation is frequently unrevealing. However, clinical experience suggests that psychiatric causes are relatively common.
This research aimed to screen for mental disorders in patients complaining of palpitation and healthy persons in order to perform a preliminary comparison between them.
Patients and This is a case-control study to screen mental disorders. The target population consisted of adult volunteers with benign palpitation and their matched healthy persons. They were referred during a 10-month-period to the cardiology outpatient’s clinic of Mostafa Khomeini hospital in Tehran, Iran. Sampling was accidental and eventually 110 participants comprised the sample size. The measuring tool was GHQ-28 (28-item general health questionnaire) and the main variable was the questionnaire score obtained from the Likert scoring method.
Comparing two groups showed that the number of participants with the scores more than cut-off point in palpitation group was significantly more than healthy person group (85.4% vs. 43.6% with P Palpitation is the most common symptom in psychiatric disorders such as anxiety and somatization disorders. According to the results of this study, psychiatric causes have an important role in Iranian patients complaining of palpitations (benign form). Considering this fact may lead to a more effective treatment of benign palpitations.

We investigated the pharmacogenetic effects of CYP2C19 polymorphisms in a group of Iranian patients with cardiovascular diseases who were on clopidogrel treatment. One hundred and eighteen Iranian patients receiving implants of coronary stents were selected, in whom the CYP2C19 681G>A polymorphism was analyzed by Restriction Fragment Length Polymorphism (RFLP)-based PCR using Sma I. Seventy-six patients with CYP2C19 (1*1*), 39 patients with CYP2C19 (1*2*), and 3 patients with CYP2C19 (2*2*) were identified. The mean serum clopidogrel concentration in patients with CYP2C19 (1*2*) polymorphism was significantly lower than the CYP2C19 (1*1*) group. However, because of the limited number of the patients in the CYP2C19 (2*2*) group, the result was not fully reliable. The results suggested that patients with CYP2C19 (1*2*) might need a higher dose of clopidegrel than that administered to patients without this polymorphism and a CYP2C19 polymorphism test could be useful in determining the dose of clopidogrel to be administered.

L-tryptophan is an important ingredient in medicines, especially in neuromedicines such as antidepressants. Many commercial processes employ various microorganisms with high tryptophan synthase activity to produce L-tryptophan from indole and L-serine, but these processes are very costly due to the costs of precursors, especially L-serine.

For this reason, we studied the ability to use processed Iranian cane and beet molasses as L-serine sources for L-tryptophan production, which enables us to reach a cost-effective process.

Whole cells of Escherichia coli ATCC 11303 were induced for L-tryptophan synthase by addition of indole to the growth medium and bacterial cells harvested from the growth medium were used as biocatalysts in the production medium. Conditions of the production medium were optimized and Iranian cane and beet molasses were processed by solvent extraction with ethanol and n-butanol and used as L-serine sources of the production medium. Amount of L-tryptophan and theoretical yield of L-tryptophan production were determined by High Performance Liquid Chromatography and by a colorimetrical method on the basis of the remaining indole assay, respectively.

L-tryptophan production increased by 15 folds, when indole was used as an inducer. L-tryptophan was produced from processed Iranian beet molasses in satisfactory amounts (0.53 mM) and no exogenous pyridoxal phosphate was required as a cofactor under our experimental conditions.

The obtained results proved that Iranian beet molasses include significant amounts of L-serine that makes them a suitable substitution for L-serine. Findings of the present study give impetus to use of Iranian beet molasses for cost-effective L-Trp production in the amino acid industry.

Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ transplantation, has a narrow therapeutic range with considerable inter-individual and intra-individual pharmacokinetic variability. To date, there is no information on the pharmacokinetics of tacrolimus in Iranian liver transplant recipients. This study was designed to determine pharmacokinetic properties of orally administered tacrolimus in Iranian adult liver transplant recipients. Tacrolimus doses and steady state whole blood trough concentrations as well as patient demographic and clinical data were obtained retrospectively using the 30 included patients’ medical records. Pharmacokinetic parameters were estimated by using a nonlinear mixed effect model program (Monolix version 3.1). Absorption rate constant was fixed at two hours-1. Drug apparent clearance (CL/F), apparent volume of distribution (Vd/F), and elimination half life (t½β) were calculated. The administered dose of tacrolimus to the patients ranged from 0.02 to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t½β were found to be 9.3 ± 0.96 L/h, 101 ± 29 L, and 7.5 hours, respectively. The pharmacokinetics of tacrolimus was highly variable among our patients. CL/F, Vd/F, and t½β of tacrolimus in this study were comparable to reported values from Italian heart transplant patients but somewhat different from reported ones from other solid organ transplant populations.

Platelets have a crucial role in homeostasis and thrombosis. Their haemostatic role is to prevent from bleeding after activation in the platelet aggregation pathway. In pathologic cases, they contribute to atherothrombosis. Antiplatelet drugs inhibit platelet aggregation so they are used successfully in treatment courses. Clopidogrel, an antiplatelet drug, is an ADP analogue. It inhibits ADP coupling with its receptor and prevents atherothrombosis. Despite its great success, some patients do not display an adequate antiplatelet response due to genetic resistance. Genetic investigations have displayed CYP2C19 polymorphism as the most prevalence factor of genetic resistance. Use of higher doses of Clopidogrel, combined antiplatelet therapies or new potent drugs is a potential alternative strategy.