Pharmacokinetics and brain penetration study of chlorogenic acid in rats

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with t_max of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC_0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC_{brain, IN}) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC_{brain, IV}) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.     

Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a focused review

Open in a separate window     

Intraoperative local anaesthesia for paediatric postoperative oral surgery pain--a randomized controlled trial

The aim of this study was to improve the pain experience for children following oral surgery under general anaesthesia. To this end, the efficacy and safety of intraoperative local anaesthetic (2% lidocaine with 1:200,000 epinephrine) for postoperative pain control was investigated. In a randomized controlled trial, 142 patients aged 12 years or less, who were scheduled for dental extractions under general anaesthesia, received local anaesthesia or saline intraoral injection after induction of anaesthesia. There was statistically no significant difference between groups for pain scores recorded preoperatively, on waking, at 30 min, at 24h, or for distress scores recorded preoperatively, on waking and at 30 min. 'Severe' pain scores were recorded for 13% of treatment and 12% of control patients and 'very severe' for 13% of treatment and 10% of control patients on waking. These rates were similar at 30 min but reduced at 24h. Lip/cheek biting injuries occurred in one control and three treatment patients. Intraoperative local anaesthesia has been found to be effective for pain control following a range of other surgical procedures, but we did not find it to be effective in reducing postoperative pain or distress in children after oral surgery. Reasons may include unfamiliarity with altered orofacial sensation.     

A double-blind randomized controlled trial investigating the effectiveness of topical bupivacaine in reducing distress in children following extractions under general anaesthesia

OBJECTIVE: This study was designed to investigate the effectiveness of topical bupivacaine (0.25%) in reducing postoperative distress following extraction of teeth under general anaesthesia in children. DESIGN: The study was a double-blind randomized controlled trial. SETTING: The study was conducted in a dental hospital. SAMPLE: The sample comprised 135 children aged between 2 and 12 years of age who were undergoing outpatient general anaesthesia for simple dental extractions. METHODS: The children were randomly allocated to one of two groups: the bupivacaine group (the study group) comprised 68 children whilst the sterile water group (the control group) comprised 67. Following the extraction of their teeth, children had swabs soaked in the appropriate solution placed over the exposed teeth sockets. A five-point face scale was employed by an independent observer to evaluate the distress for each child. Evaluation of distress was made preoperatively, on recovery from the general anaesthetic, and again, 15 min following recovery from the anaesthetic. RESULTS: There were no statistically significant differences between the mean distress scores for the bupivacaine and sterile water groups preoperatively, postoperatively or 15 min postoperatively. For both groups, however, there were significant increases in distress scores between the preoperative and 15 min postoperative assessment scores. CONCLUSION: Extraction of teeth under general anaesthesia does cause distress in children. There is no evidence that topical bupivacaine reduces this distress when compared to sterile water.     

Anti-inflammatory activity of sappanchalcone isolated from Caesalpinia sappan L. in a collagen-induced arthritis mouse model

Archives of Pharmacal Research - Sappanchalcone, a bioactive flavonoid isolated from the heartwood of Caesalpinia sappan L. possesses anti-inflammatory effects. We studied the efficacy of...     

Eosinophilia: secondary, clonal and idiopathic

Blood eosinophilia signifies either a cytokine-mediated reactive phenomenon (secondary) or an integral phenotype of an underlying haematological neoplasm (primary). Secondary eosinophilia is usually associated with parasitosis in Third World countries and allergic conditions in the West. Primary eosinophilia is operationally classified as being clonal or idiopathic, depending on the respective presence or absence of a molecular, cytogenetic or histological evidence for a myeloid malignancy. The current communication features a comprehensive clinical summary of both secondary and primary eosinophilic disorders with emphasis on recent developments in molecular pathogenesis and treatment.     

Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high‐risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta‐analysis (3940 melanoma cases and 3620 controls) with two‐side p values of 0.002, (OR = 0.86) and 4.07 × 10^?10 (OR = 0.80), respectively. Exome sequencing revealed a non‐synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.     

An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.     

Sentinel Lymph Node Localization Using 1 % Isosulfan Blue Dye in Cases of Early Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

To study the use of 1 % isosulfan blue dye in identifying sentinel node, sensitivity and specificity of frozen section and predictive value of sentinel node in predicting other nodal status in the cases of oral cavity and oropharyngeal squamous cell carcinoma. 15 patients of oral cavity and oropharyngeal SCC with clinically N0 neck, who required WLE of the primary lesion as well as neck dissection as per recommended treatment protocol, were selected from OPD. 1 % Isosulfan dye was injected peritumorally intraoperatively after the induction of general anaesthesia. Neck dissection was performed and first node taking up the blue dye was identified, dissected, removed and was sent for frozen section. In two of the 15 cases a sentinel node was identified (sensitivity of the technique—13 %). Both the sentinel nodes were positive for presence of metastasis on final histopathology (specificity—100 %). However, five cases had nodal metastasis on final histopathological examination of the neck dissection specimen (sensitivity of sentinel lymph node biopsy—40 %). Frozen section examination had a sensitivity and specificity of 100 %. All data was analyzed using SPSS 16 software. Use of 1 % Isosulfan Dye for identification of sentinel node is a simple and cheap technique, however, it has low sensitivity as compared to the use of triple diagnostic procedure consisting of lymphoscintigraphy, per op gamma probe localization and using isosulfan dye for sentinel node identification. Sentinel lymph node is representative of nodal status and correlates well with the final histopathological examination of the dissected neck nodes.