Therapeutic efficacy and safety results of 177Lu-PSMA therapy in metastatic castration-resistant prostate cancer patients: first experience of a developing South Asian Country.

OBJECTIVE: Metastatic castration resistant-prostate cancer (mCRPC) is deadly condition that remains incurable despite various therapies. Initial studies have shown promising results with Lutetium-177 prostate-specific membrane antigen ( 177 Lu-PSMA) therapy for advanced prostate cancer. However, most of the published efficacy and safety data is retrospective. The purpose of the study was to prospectively evaluate the therapeutic efficacy and safety results of 177 Lu-PSMA therapy in mCRPC patients after 2 cycles. METHODS: Twenty-five patients of mCRPC, treated with standard care treatment were enrolled for 2 cycles of 177 Lu-PSMA therapy. Prostate-specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, Visual Analogue Score (VAS) and Analgesic Quantification Scale (AQS) for efficacy and hemoglobin, total leukocyte, platelets and serum creatinine for toxicity were recorded pre and post-therapy. Paired sample t-test was used for statistical analysis. RESULTS: Treated patients with mean PSA level of 157 ng/ml received mean dose of 6.84 GBq of 177 Lu-PSMA. For PSA, partial response (PR) was seen in 11/25 (44%), stable disease (SD) in 8/25 (32%) and progressive disease (PD) in 6/25 (24%) patients. Grade 1 and 2 hemoglobin toxicity was seen in 5/25 (20%) and 6/25 (24%) patients respectively. No patient developed grade 3 or 4 bone marrow toxicities. Grade 1 and 2 nephrotoxicity was seen in 1 patient each. Statistically significant difference was seen in ECOG, VAS and AQS scores ( P  < 0.001). No significant nephrotoxicity was observed ( P  = 0.558). CONCLUSION: Efficacy and safety of 177 Lu-PSMA therapy after 2 cycles have shown significant PSA response and pain palliation in heavily pretreated mCRPC patients.

Diagnostic value of strain elastography and shear wave elastography in differentiating benign and malignant breast lesions.

BACKGROUND: Conventional B-mode breast ultrasonography, though the primary modality to determine benign or malignant nature of a solid breast lesion, sometimes encounters overlapping sonographic morphological features in a single lesion. Elastography leads to improvement by evaluating the structural aspects and characterization of the lesion as benign or malignant on the basis of multi-parametric assessment. OBJECTIVE: Determine the role of strain elastography (SE) and shear wave elastography (SWE) in differentiating benign and malignant breast lesions. DESIGN: Cross sectional SETTING: Radiology department of hospital PATIENTS AND METHODS: Patients meeting inclusion criteria referred to our hospital for ultrasonography followed by biopsy or surgical excisions were examined with B-mode ultrasonography and by both strain and shear wave elastography. MAIN OUTCOME MEASURES: Mean values of SE and SWE in benign and malignant breast lesions, determination of cutoff using AUC curves and sensitivity and specificity of both techniques. SAMPLE SIZE: One hundred breast lesions from 95 consecutive patients. RESULTS: The mean (SD) strain elastography ratio in the overall patient population was 4.1 (2.0). Cutoff for benign vs. malignant lesions was 2.86 on the ROC curve. The AUC was 0.911 (95%CI; 0.835-0.988: SE, 0.039) with a sensitivity of 95.8% and a specificity of 89.3%. For the SWE kPa values, the ROC curve showed the AUC was 0.929 (95% CI, 0.870-0.988; SE: 0.030, P<.001). Assigning 45.3 as a cut off value provided a sensitivity of 95.8% with a specificity of 85.7%; the positive predictive value was 94.5% and the negative predictive value was 89.6%. The Breast Imaging Reporting and Data System (BI-RADS) category alone was able to differentiate between benign and malignant lesions with a sensitivity of 91.7% and a specificity 100% keeping the cut off value between 4a and 4b. The area under the ROC curve was 0.979. Combining the three (BI-RADS + SE + SWE) distinguished benign vs. malignant lesions with a sensitivity up to 100% and specificity up to 96.3%. CONCLUSION: Combining SE and SWE as a complementary tool with conventional B-mode ultrasonography has a significant potential for better characterization of solid breast lesions and decreasing unnecessary biopsies of BI-RADS IVa lesions. LIMITATIONS: Single institution study. CONFLICT OF INTEREST: None.

Early postoperative recurrences for colon cancer: Results from a Pakistani rural cohort.

OBJECTIVES: We conducted this study to determine the factors associated with early postoperative recurrence in colon cancer patients treated with curative intent. METHODS: All consecutive patients who underwent curative resection for colon cancer between January 2014 and December 2016 were reviewed. All patients received either adjuvant chemotherapy or follow-up at the Bannu Institute of Nuclear Medicine Oncology and Radiotherapy (BINOR). The patients lived in rural areas of southern Khyber Pakhtunkhwa province. RESULTS: We enrolled 72 patients, 28 of whom experienced a postoperative recurrence within 2 years (early recurrence). In univariate analysis, postoperative early relapse was significantly correlated with advanced age (>60 years, p = 0.030), nodal status (p = 0.012), pathological stage (p = 0.013), number of nodes removed (p < 0.001), and perineural invasion (p = 0.044). In multivariate analysis, age more than 60 years (p = 0.031) and fewer than 12 lymph nodes removed (p = 0.003) were independent predictors for early recurrence. The liver was the most common site of recurrence (42.8%) in this study. CONCLUSION: Our results showed that advanced age and the removal of fewer than 12 lymph nodes during surgery were significant predictors for early postoperative recurrence. Identification of high-risk patients during follow-up with enhanced therapeutic modalities can improve disease-free survival.

Acute Side Effects with High Dose Rate Computed Tomography-guided Three-dimensional Brachytherapy in Carcinoma Cervix.

OBJECTIVES: To determine the frequency and grades of acute side effects with three-dimensional brachytherapy in carcinoma cervix using RTOG/EORTC acute radiation morbidity scoring criteria. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Radiotherapy, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Pakistan from July 2016 to September 2017. METHODOLOGY: A total of 55 histologically proven patients of squamous cell carcinoma of the cervix, aged between 16-70 years, were included. Patients with previous radiotherapy in pelvic area, inflammatory bowel diseases and known diabetics, were excluded. All patients were given a radiation dose of 7 Gray in 4 insertions through 3-dimensional conformal brachytherapy planning. Acute vaginal, gastrointestinal, and genitor-urinary side effects of brachytherapy were assessed. RESULTS: Mean age of the patient population was 47.09 ±13.10 years (Range: 21-68). Mean time to presentation was 5.65 ±2.32 months and mean tumor size was 3.67 ±1.47 cm. Majority, i.e. 18 (32.7%) patient presented in stage III. Most of the patients, 26 (47.3%), had ECOG-2 performance status. Grade-1 genitourinary toxicity was significantly high (p <0.001). In lower gastrointestinal toxicity, Grade-1 was the highest being 54.5%. Conversely, vaginal toxicities of grade-2 and 3 were most commonly seen. Stratification of acute side effectswith respect toage, stage and tumor size revealed no significant association except in mucosal membrane toxicity, which was affected by tumor size (p = 0.004). CONCLUSION: Three-dimensional brachytherapy in carcinoma cervix is a safe and tolerable procedure with minimal acute side effects. Key Words: Cervical cancer, Brachytherapy, Acute toxicities, Computed tomography.

Strain Elastography for Differentiation between Benign and Malignant Thyroid Nodules.

OBJECTIVE: To find out the diagnostic accuracy of strain elastography in differentiating between benign and malignant thyroid nodules taking cytology as a gold standard. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Radiology Department, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Pakistan, from February to July 2019. METHODOLOGY: A total of 110 patients aged 18-80 years of either gender having one or more solid nodules, in thyroid lobe on conventional ultrasound examination, were included. Patients with cystic nodules, nodules that constitute more than 75% volume of thyroid lobe and thyroid nodules with peripheral calcification were excluded. All the patients then underwent strain ultrasound elastography with high-resolution unit equipped with a linear array probe which was centered at 7.5 MHz. Sonoelastographic findings were correlated with cytology. RESULTS: Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of sonoelastography in differentiating between benign and malignant thyroid nodules taking cytology as gold standard was 90.0%, 90.0%, 91.53%, 88.24% and 90.0%, respectively. Optimal cutoff to differentiate between malignant and benign nodules for elasticity strain using ROC curve was 2.57. Area under the curve (AUC) was found to be 0.933 (0.879-0.987) p<0.001. CONCLUSION: Sonoelastography is the non-invasive modality of choice with high diagnostic accuracy in differentiating between malignant and benign nodules. Key Words: Sonoelastography, Strain elastography, Thyroid nodule, Benign, Malignant, Sensitivity, Specificity.

THE Role of Preoperative carcinoembryonic antigen in recurrence of resectable colorectal carcinoma.

In colorectal carcinoma, carcinoembryonic antigen (CEA) is a recommended marker for surveillance after curative resection. The aim of the present study was to determine the association of preoperative CEA with recurrence of colorectal carcinoma in our population. The study included 55 patients with all operable stages of colorectal adenocarcinoma treated during the 2012-2014 period, evaluated retrospectively and followed-up for recurrence for 2 years. Data on the baseline (preoperative) CEA levels were retrieved from patient files. On data analysis, SPSS 16.0 was used. In patients with normal preoperative CEA, the rate of recurrence was significantly low (p=0.008) and the likelihood of no recurrence 1.55-fold greater as compared to patients with raised initial CEA levels (p=0.028). In patients with raised preoperative CEA, the risk of recurrence was 5.26-fold greater as compared to those with normal CEA levels (p=0.028). A significant weak positive correlation (rs=0.297) was found between raised CEA and recurrence. A highly significant (p=0.002) moderate positive correlation was recorded in patients aged <50 and moderate positive correlation of borderline significance in males (rs=0.324, p=0.058). Sensitivity was 94.4% and specificity 32.4% in predicting recurrence. Accordingly, preoperative elevated CEA showed a significant weak positive correlation with recurrence while normal preoperative CEA moderately decreased the likelihood of recurrence.

Smokeless tobacco use and risk of oral cavity cancer

Background/aim/AIM: Smokeless tobacco has been associated with oral cavity cancer for several decades. The incidence of oral cavity cancer is higher in some parts of the world especially South and South-East Asia including Pakistan. The aim of current study was to evaluate the risk of oral cavity cancer among smokeless tobacco users in our country. Materials and methodsAND METHODS: A case-control study was conducted between November 2016 and September 2017. Patients diagnosed with oral cavity cancer receiving treatment were included as cases and the attendants of various cancer patients visiting the hospital during the study period were included in the study as controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and all reported P-values were considered significant at < 0.05. Results: The crude OR for the "ever smokeless tobacco users" among cases and controls came out to be 4.98 (95%CI; 2.76­9.01). The OR for snuff users among cases and controls was 4.82 (95%CI; 2.37­9.80) and that for betel leaf users was 4.42 (95%CI; 1.66­11.91) after adjusting for smoking and age. Conclusion: Our study provided strong evidence for snuff and betel leaf to be independent risk factors for oral cavity cancer.

Sonographically guided metalic clip placement for tumour localization in early breast cancer patients undergoing neoadjuvant chemotherapy.

OBJECTIVE: To determine the outcome of sonographically-guided indigenous low-cost metallic clip placement for tumour localisation in patients of early breast cancer undergoing neoadjuvant chemotherapy. . METHODS: The prospective analytical study was conducted at the Institute of Nuclear Medicine and Oncology, Lahore, Pakistan, from May 2016 to December 2017, and comprised biopsy-proven breast cancer cases. Under sonographic guidance, metallic clips were placed as markers within the lesions before their scheduled preoperative neoadjuvant chemotherapy. The procedure was performed using an 18 gauge lumbar puncture needle and 25 gauge needle by a locally devised simple and cost-effective technique. Post-procedure mammography was performed to confirm the location of clips within the lesions and to evaluate its role in imaging assessment of treatment response after neo adjuvant chemotherapy. SPSS 20 was used for data analysis. RESULTS: There were 30 women with a mean age of 40.43+11.35 years (range: 21-60 years). These women had 32 lesions with a mean size of 26.72+9.85mm (range: 8-58mm). Breast conserving surgery was performed on 28(87.5%) lesions and negative margins were achieved in all these cases. Modified radical mastectomy was performed on 4(12/5%) non-responding lesions. No complication was noted in association with metallic clip placement, and the clips were easily visualised on mammograms without causing any interference with treatment response. CONCLUSIONS: Sonographically-guided metallic clip placement by a simple indigenously devised technique before neoadjuvant chemotherapy was found to be a well-tolerated, safe and cost-effective method for accurate preoperative localisation of tumour bed and to assess response to therapy.

Tumour sidedness and clinicopathological features of resected colon cancer in rural population of Northern Pakistan: single institutional analysis / Lateralidade tumoral e características clínico-patológicas do câncer de cólon ressecado na população rural do norte do Paquistão: análise em uma única instituição

ABSTRACT Objectives: Different clinicopathological and molecular features have been demonstrated between right and left sided colon cancers. We aimed to characterize colon cancer and sidedness among a North-Pakistani rural population diagnosed with colon cancer in our institution. Methods: Seventy patients were included in the study that received adjuvant chemotherapy at Bannu Institute of Nuclear Medicine Oncology and Radiotherapy) Bannu, Pakistan from January 2014 to December 2017. Chi-square test was used for significance of categorical variables. p-Values less than 0.05 were considered significant. Results: Mean age at diagnosis for right side colon cancer patients was 43.94 years and for left side colon cancer, it was 49.83 with no significant difference. Male patients were presented more with right (77% vs. 54%, p = 0.044) and females with predominantly left sided tumours i.e. (46% vs. 23%, p = 0.044). Right sided cancer tended to be more poorly differentiated (20% vs. 0%, p = 0.020). Mucinous adenocarcinoma was seen mostly in right sided colon cancer (37% vs. 3%, p ≤ 0.001). There were more locally advanced presentation of right side colon cancer with more node positive (83% vs. 60%, p = 0.025) and lymphovascular invasion (51% vs. 37%, p = 0.016). Sigmoid colon was the most common tumour subsite involved. Conclusion: Our study is the first report of colon cancer in a rural population in North-Pakistan. An earlier onset of tumours (44-50 years) was observed in comparison with global data.

RESUMO Objetivo: Características clínico-patológicas e moleculares distintas foram observadas em tumores de cólon no lado direito ou esquerdo. O presente estudo teve como objetivo caracterizar o câncer de cólon e sua lateralidade em uma população rural norte-paquistanesa diagnosticada com câncer de cólon nesta instituição. Métodos: O estudo incluiu 70 pacientes que foram submetidos a quimioterapia adjuvante no Instituto Bannu de Medicina Nuclear Radioterapia Oncológica (BINOR), Bannu, Paquistão, entre janeiro de 2014 e dezembro de 2017. O teste qui-quadrado foi utilizado para mensurar a significância das variáveis categóricas. Valores de p menores que 0,05 foram considerados significativos. Resultados: A média de idade ao diagnóstico entre pacientes com câncer de cólon no lado direito foi de 43,94 anos e entre aqueles com câncer de cólon no lado esquerdo, 49,83, sem diferença significativa. Os pacientes do sexo masculino apresentaram mais tumores no lado direito (77% vs. 54%, p = 0,044) e as pacientes do sexo feminino apresentaram mais tumores no lado esquerdo (46% vs. 23%, p = 0,044). Tumores mal diferenciados foram mais comumente observados no lado direito (20% vs. 0%, p = 0,020). Adenocarcinoma mucinoso foi observado principalmente em casos de tumores no lado direito (37% vs. 3%, p ≤ 0,001). A apresentação local estava mais avançada em tumores de cólon no lado direito, com mais linfonodos positivos (83% vs. 60%, p = 0,025) e invasão linfovascular (51% vs. 37%, p = 0,016). O cólon sigmoide foi o sublocal mais comum. Conclusão: O presente estudo é o primeiro relato de câncer de cólon em uma população rural no norte do Paquistão. Em comparação com dados globais, observou-se um surgimento mais precoce dos tumores (44-50 anos).

Epidemiology and Treatment Outcomes of Sinonasal Tumors: A Single Institute's Experience in Pakistan.

OBJECTIVE: To find the epidemiology and risk factors of sinonasal tumors and treatment outcomes in squamous cell carcinoma. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: The Institute of Nuclear Medicine and Oncology Lahore (INMOL), Lahore, from May 2016 to March 2017. METHODOLOGY: All histopathologically proven cases of paranasal sinuses and nasal cavity were selected from the hospital record for epidemiological analysis. Survival outcomes of patients with squamous cell histopathology were determined, which is commonly occurring type. Relevant information was obtained from patient record and telephone communication. The data were analysed using SPSS V.20. RESULTS: Sinonasal malignancies are rare, making (n=81) 0.2% of all registered tumors; out of which, 46 (56.7%) had squamous cell histology. Median age was 50.0 years (IQR: 60.7-40.0) with male predominance (1.7:1). Most of patients presented at advanced stage, T3/ T4 in more than two-thirds of cases, and associated with nodal metastasis in 43.5% of squamous cell carcinoma. In patients with squamous cell histology, median disease-free survival was 19.00 months (SE: 1.65, 95% CI, 15.75 - 22.25), median overall survival remained 34.00 months (SE: 1.84, 95% CI, 30.00 - 38.00). Nodal status had significant effect (p<0.001) on survival. Radiotherapy had significant effect on improved survival (p=0.001) and distant metastasis remained negative prognostic factor (p=0.001). Disease stage was also significantly associated with overall survival (Log Rank 0.014). Tumour size, surgery, chemotherapy, and chemoradiotherapy were not significantly associated with survival. Cumulative survival at 1, 2, and 3 years was 87%, 48% and 29%, respectively. CONCLUSION: Sinonasal malignancies are rare, advanced stage is common, and radiotherapy improves overall survival.

Disease Characteristics and Treatment Outcome of Testicular Germ Cell Tumors Treated with Platinum-Based Regimens.

OBJECTIVE: To determine the disease characteristics of testicular germ cell tumor, biochemical/radiological response to chemotherapy and common toxicity profile. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from January 2010 to December 2013. METHODOLOGY: Fifty-one patients with histologically proven testicular germ cell tumor, who fulfilled the pre-defined eligibility criteria, were selected. Presenting symptoms and disease stage were studied. Patients were staged according to the AJCC 2010 staging criteria and prognosis was classified according to the IGCCCG Classification of Metastatic Germ Cell Cancer. Initial chemotherapy treatment was based upon the International Germ Cell Consensus Classification, 1997. Patients were also evaluated for chemotherapy-induced toxicity based on Common Toxicology Criteria version 4. SPSS version 16.0 was used for statistical analysis. RESULTS: Main presenting symptoms included testicular pain (37.3%), testicular swelling (25.5%), and abdominopelvic pain (11.8%). Most of the patients had mixed germ cell histology (p <0.001) and presented with advanced disease stage. Out of 51 patients, 41 (80.3%) achieved complete clinical remission after first line chemotherapy. All patients having complete response achieved 2-year survival and 37 (90.2%) had no evidence of recurrent disease. Four patients with recurrent disease achieved complete remission with second line chemotherapy. Five (9.8%) had partial response after first line chemotherapy while 2 (3.9%) progressed on treatment. All patients developed alopecia, 21 (41.1%) experienced other toxicities which were managed symptomatically and with minor dose modifications. CONCLUSION: Many patients with germ cell tumors presented with pain, and in an advanced stage, with mixed histology. Overall response rate was 90.2% with platinum-based chemotherapy.

Studying the efficacy of escalated dose conformal radiation therapy in prostate carcinoma - Pakistan experience.

BACKGROUND: Our objective in this study was to evaluate the role and benefits in terms of local toxicity and biochemical disease-free survival (bDFS) following escalated-dose conformal radiation therapy in prostate adenocarcinoma. METHODS: The study population was composed of 53 patients with histologically proven T1b-T4, NO, MO prostate adenocarcinoma, having any Gleason score with prostate-specific antigen (PSA) of less than 50 ng/mL at diagnosis, given escalated dose EBRT (74 Gy) during the period between January 2011 and December 2013, retrospectively and evaluated for a period of 2 years post-radiation. Patients were followed up for a period of 2 years, beginning after completion of escalated dose external beam radiotherapy (EBRT) for biochemical failure as defined in ASTRO consensus committee guidelines 1996 and investigated for gastrointestinal, genitourinary skin toxicity. RESULTS: Out of 53 patients, 35 showed no biochemical failure at the end of 2 years following the completion of definitive escalated dose conformal radiotherapy while 18 were observed to have biochemical relapse. Acute gastrointestinal grade 1 toxicity was found in 26 patients, grade 2 in 24, and grade 3 only in 3 patients. Late gastrointestinal grade 0 toxicity was found in 16 patients, grade 1 in 28, grade 2 in 7 and grade 3 only in 2 patients. Grade 1 acute genitourinary toxicity was the highest in frequency observed in 28 of the total population followed by grade 2 in 21, grade 0 and grade 3 each, only in 2 patients. Late genitourinary Grade 0 toxicity was observed in 32 patients, grade 1 in 19, grade 2 and 3 only in 1 patient of the total population, respectively. CONCLUSION: Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity.

Efficacy and Toxicity of Concurrent Chemoradiation in Inoperable Oral Carcinoma in Pakistani Population.

OBJECTIVE: To evaluate the efficacy of concurrent chemoradiation in patients with locally advanced inoperable squamous cell carcinoma of oral cavity in terms of local control and toxicity. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from January 2008 to December 2013. METHODOLOGY: Sixty-nine patients with locally advanced inoperable oral cavity cancer, registered in INMOL hospital from January 2008 to December 2013 who fulfilled a pre-defined eligibility criteria, were enrolled in the study. Concurrent chemoradiation protocol consisted of conventional fractionation delivering 70 Gy with weekly Cisplatin (50 mg/m2) during the course of radiation. Tumor response was calculated by RECISTcriteria version 1.1 along with the median overall survival and disease-free survival. Acute treatment related toxicities were graded as (G). RESULTS: Thirty-six (52.17%) patients showed complete response; while 19 (27.54%), 8 (11.59%) and 6 (8.7%) were observed with partial response, stable and progressive disease, respectively. Treatment response was significant (p<0.001) in terms of responders vs. non responders to treatment. Median overall survival was 18.00 months; whereas, median disease-free survival remained 14.00 months. Main toxicities included mucositis (G3 and G4, 71%), xerostomia (G2 and G3, 82.5%), vomiting (G3 and G4, 51%), myelosuppression (G3 and G4, 26.2%), dermatitis (G3 and G4, 49.2%), and fatigue (G3 and G4, 57.9%). CONCLUSION: Platinum based CCR Tremained effective for inoperable oral cancer patients.

Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain Barrier.

Brain, the centre of the nervous system and an integral part the body, is protected by two anatomical and physiological barriers- Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB). Blood-Brain Barrier is a very complex and highly organized multicellular structure that shields the brain from harmful substances and invading organisms from the bloodstream and thus offering protection against various brain diseases and injuries. However, it also impede the effective delivery of drug to the brain, thus, preventing treatment of numerous neurological disorders. Even though various traditional approaches such as Intra-Cerebro-Ventricular (ICV) injection, use of implants, disruption of BBB and use of prodrugs have achieved some success in overcoming these barriers, researchers are continuously working for promising alternatives for improved brain drug delivery. Recent breakthroughs in the field of nanotechnology provide an appropriate solution to problems associated with these delivery approaches and thus can be effectively used to treat a wide variety of brain diseases. Thus, nanotechnology promises to bring a great future to the individuals with various brain disorders. This review provides a brief overview of various brain drug delivery approaches along with limitations. In addition, the significance of nanoparticles as drug carrier systems for effective brain specific drug delivery has been highlighted. To show the complexity of the problems to be overcome for improved brain drug delivery, a concise intercellular classification of the BBB along with general transport routes across it is also included.

Effect of an anti-thyroid drug, 2,8-Dimercapto-6-hydroxy purine on reproduction in male rats.

This histomorphological study is designed to evaluate the peripheral action of 2,8-Dimercapto-6-hydroxypurine (an antithyroid drug) on male reproductive system. The drug was administered as i.p. injection for 21 days to investigate its role on morphology of intratesticular cells and plasma testosterone level. Adult male rats (n=12), divided into three groups i.e. control, dimethylsulphoxide (DMSO) and 2,8-Dimercapto-6-hydroxypurine treated groups and treated with saline, DMSO and 2,8-Dimercapto-6-hydroxypurine for 21 consecutive days respectively. Blood samples were collected at day 1, 7, 14 and 21 and analyzed by using EIA systems. All the animals were scarified on 22nd day and testicular tissues were studied by histomorphpological assesment. 2,8-Dimercapto-6-hydroxypurine caused a significant decrease (P<0.0001) in mean testicular cell population, testicular cell diameter and resulted in arrested spermatogenesis. A significant decrease (P<0.0001) was observed in mean Sertoli and Leydig cell population and diameter in treated group. Similarly a significant decrease was observed in plasma testosterone levels at days 1, 7 and 14 (P<0.05) and further decrease by day 21 (P<0.01) of drug treatment. The present study suggests that 2,8-Dimercapto-6-hydroxypurine is a negative modulator of reproductive system as it suppressed the plasma testosterone level and proliferation of different testicular cell types in adult male rats.

Essential and toxic elements in three Pakistan's medicinal fruits (Punica granatum, Ziziphus jujuba and Piper cubeba) analysed by INAA.

Three important medicinal fruits generally used by the people of Pakistan for the treatment of different diseases have been studied for their mineral contents. Twenty-two major and minor trace elements (essential, toxic and non-essential) were identified in Punica granatum (pomegranate), Ziziphus jujuba (jujube) and Piper cubeba L. (cubeb) by employing instrumental neutron activation analysis technique. The studied medicinal herbs are a good source of the essential elements while toxic elements are found in trace amounts. K is detected as a major element in pomegranate, jujube and cubeb with respective values of 1.20%, 1.18% and 2.01%. Pomegranate has significant concentrations of Na, Zn, Cr and Se; jujube has high Cl, Zn, Mn and Co contents while cubeb is a good source of K and Fe. The baseline data presented in this work can be used in understanding the role of mineral elements in nutritive, preventive and therapeutic properties of medicinal herbs.

6-Benzyl-sulfanyl-9H-purine.

The phenyl ring of the title compound, C(12)H(10)N(4)S, a purine derivative, is oriented at a dihedral angle of 76.65 (6)° with respect to the purine ring system. An inter-molecular N-H⋯N hydrogen bonds stabilizes the crystal structure.