Ecotoxicity, Health Risks and Contact Allergy Due to p-Phenylenediamine in Hair Dyes and Tattoos: Female Students' Perspectives.

While the financial advantages of hair coloring and tattooing are widely acknowledged, environmental hazards and health risks linked to this trend due to their p-phenylenediamine (PPD) content have received less attention. Health education on hair-dying products is warranted to enhance the public's awareness of hair-dying ingredients and their side effects.  A cross-sectional study was therefore conducted with 319 students to assess knowledge of ecotoxicity, health risks, and practices of hair dyeing and tattooing among undergraduate students. A random sample of 59 students was checked for any allergic morphology in the scalp and exposed areas of skin near the neck, ears, palms, and nails. Responses collected were used for data analyses using IBM SPSS Statistics for Windows, Version 17 (Released 2008; IBM Corp., Armonk, New York, United States). Use of hair dye was significantly high among study participants 58.5% (n=187; p<0.05). However, their knowledge regarding the presence of PPD in hair dyes and associated environmental toxicity (37.8%, n=121) was very limited. The majority of participants did not do any allergy tests before applying hair dye (88.9%, n=283). The study revealed that the main reason for hair coloring was as a fashion statement (93.7%, n=299). Regarding tattooing practices, 96.9% (n=309) of study participants had never practiced tattoos, and hence, the prevalence of tattooing was 3.9% (n=12). These data confirmed that the practice of hair dyeing as a style statement was high among students. However, the majority were unaware of their PPD contents and their potential ecotoxicity and health risks.

Awareness of sickle cell disease among nursing undergraduates in Farasan: Its interference with malaria.

Aim: The present study was conducted to generate data on awareness and incidence of sickle cell disease (SCD) and also to adduce the widespread myths peddled about SCD. Materials and Methods: Students studying in the Department of Nursing were recruited. A pretested, self-administered sickle cell assessment questionnaire was distributed electronically through WhatsApp group to collect necessary data. Participants were screened for malaria by thin blood smear analyses, and their hemoglobin (Hb) contents (g/dL) were determined by Sahli's haemoglobinometer. Statistical analyses were done using Origin (version 8.1, USA). A reliability study was performed for the validity of questionnaire data. Results: Study participants had significantly high awareness regarding SCDs (89.9%, P < 0.001). Most participants (96.3%) were aware about government policy regarding premarital screening for genetic disorders and replied that the government has strict health policies backed by equally robust laboratory diagnostics. Moreover, none of the participants had SCDs, although their parents had a consanguineous marriage. Thin blood smear analyses of participants did not reveal any cases of Plasmodium falciparum. However, significant percentages (33.1%) were found to be anemic, probably due to their dietary habits and lifestyles, as has been reflected by questionnaire analyses. Furthermore, a very less number of students had knowledge about genetic variations that might occur in malaria-endemic regions after long exposure to offer protection from malaria. Knowledge about management practices was also lacking among study participants (29%). Conclusion: This research points to the necessity that the nursing study plan should focus on providing specific training on management skills and preventive measures for SCDs, which is of paramount importance.

Contemporary Insights into Intractable Epilepsy in Children.

While most children with epilepsy find their seizures manageable through medication, some continue to experience seizures despite trying multiple drugs. Failure of medical treatment often becomes apparent early on, and for these cases, it is advisable to seek further treatment options at a specialized epilepsy center. Such centers offer additional treatments like epilepsy surgery, vagus nerve stimulation, and ketogenic diets. There is no universal definition for what constitutes "medically intractable" epilepsy. A proposal by a task force from the International League Against Epilepsy suggests that drug-resistant epilepsy could be defined as the inability to control seizures even after two adequate treatment attempts with well-chosen and tolerated medications, either alone or in combination. In this review, the authors discussed the management of intractable epilepsy in children.

Knowledge of Non-Invasive Biomarkers of Breast Cancer, Risk Factors, and BSE Practices Among Nursing Undergraduates in Farasan Island, KSA.

Background of the Study: Mammograms are sometimes met with issues of overdiagnosis and underdiagnosis; therefore, they are less reliable in identifying cancer in women with dense breasts. As a result, it is critical to be aware of other sensitive screening techniques for the early diagnosis of breast cancer. Aim: The ultimate objective of this study was to assess the knowledge of nursing undergraduates regarding non-invasive biomarkers, such as volatile organic compounds in breath, nipple aspirate fluid, sweat, urine, and tears, for the early detection of breast cancer to help improve patient care, determine the risk factors, and encourage practice of breast self-examination. Methods: Cross-sectional research was done in the Department of Nursing at Farasan campus using a self-structured questionnaire as the study tool. A total of 260 students willingly participated. The study tool had evaluation questions focused on the non-invasive biomarkers of breast cancer, risk factors, and breast self-examination practices to collect data. The data were subjected to descriptive and inferential statistics. The statistical significance was calculated at P < .05. Data analyses were done using Microsoft Excel (2013). Results: A significant knowledge gap existed among the study participants about the non-invasive biomarkers of breast cancer. A lesser percentage of students (25%) stated that they do breast self-examination on a monthly basis. The most common reasons for not doing the breast self-examination were "not knowing how to do the breast self-examination" (77.3%), fear of a positive diagnosis (53.9%), thinking that they are not at risk as all were in their teens and hence not required (44.7%), and lack of time (48.7%). Age and frequency of breast self-examination were significantly associated (P < .05) as those few students (22.7%) who were doing breast self-examination practices every 2-4 months belonged to a higher study year. Furthermore, knowledge regarding incidence rates and health care expenditure by the government on breast cancer was also significantly low (P < .05). Conclusions: Outcomes would help prioritize actions to help future nurses better understand breast cancer, allowing them to extend patient care in the best way possible.

Effectiveness of simulation-based paediatric cardiopulmonary resuscitation training program among nursing students in Saudi Arabia.

The main objective of this study was to adopt a simulation-based advanced cardiac life support training program to assess nursing students' level of knowledge and practice regarding paediatric advanced cardiac life support and to identify the major knowledge and practice gaps. The methods used in this study were pre-experimental, one group pre and post-test investigation. This study was conducted between September 2022 and November 2022, at the University College of Farasan in the Kingdom of Saudi Arabia. Quantitative data were obtained using the "Cardio Pulmonary Resuscitation Knowledge Questionnaire", "Students' Satisfaction and Self-Confidence Scale," and the "CPR Skill Checklist," which were applied to 75 participants in focus groups. Before the simulation-based CPR training, the students' mean pre-test Paediatric CPR knowledge score was 6.5±2.3 out of 42.0. After the simulation, the mean post-test CPR knowledge score (38.1±2.9) considerably improved (p 0.05). The mean post-test CPR skills score (44.7±1.2) was also considerably higher than the mean pre-test CPR skills score (11.4±2.8) at (p 0.05). Additionally, after the simulation training, students' happiness and confidence levels (61.9±2.2) greatly increased. Themes from the qualitative data showed that the simulation was viewed as an engaging and effective teaching tool by the students. Two themes emerged from the study: "Worries before simulation" and "Satisfaction after simulation". Simulation-based paediatric cardio Pulmonary resuscitation training program has raised nursing students' level of expertise in knowledge, performance, and self-efficacy. Additionally, strong satisfaction and self-confidence levels were discovered following the simulation training.

L'objectif principal de cette étude était d'adopter un programme de formation avancé en réanimation cardiaque basé sur la simulation pour évaluer le niveau de connaissances et de pratique des étudiants en soins infirmiers en matière de réanimation cardiaque avancée en pédiatrie et pour identifier les principales lacunes en matière de connaissances et de pratique. Les méthodes utilisées dans cette étude étaient des enquêtes pré-expérimentales, pré- et post-test sur un groupe. Cette étude a été menée entre septembre 2022 et novembre 2022, au Collège universitaire de Farasan, au Royaume d'Arabie saoudite. Des données quantitatives ont été obtenues à l'aide du « Questionnaire de connaissances sur la réanimation cardio-pulmonaire ¼, de l'« Échelle de satisfaction et de confiance en soi des étudiants ¼ et de la « Liste de contrôle des compétences en RCR ¼, qui ont été appliquées à 75 participants dans des groupes de discussion. Avant la formation en RCR basée sur la simulation, le score moyen des étudiants en matière de connaissances en RCR pédiatrique avant le test était de 6,5 ± 2,3 sur 42,0. Après la simulation, le score moyen de connaissances en RCR post-test (38,1 ± 2,9) s'est considérablement amélioré (p = 0,05). Le score moyen des compétences en RCR après le test (44,7 ± 1,2) était également considérablement plus élevé que le score moyen des compétences en RCR avant le test (11,4 ± 2,8) à (p 0,05). De plus, après la formation par simulation, les niveaux de bonheur et de confiance des étudiants (61,9 ± 2,2) ont considérablement augmenté. Les thèmes issus des données qualitatives ont montré que la simulation était considérée comme un outil pédagogique engageant et efficace par les étudiants. Deux thématiques sont ressorties de l'étude : « Les soucis avant la simulation ¼ et « La satisfaction après la simulation ¼. Le programme de formation en réanimation cardio-pulmonaire pédiatrique basé sur la simulation a élevé le niveau d'expertise des étudiants en soins infirmiers en termes de connaissances, de performance et d'auto-efficacité. De plus, de forts niveaux de satisfaction et de confiance en soi ont été découverts à la suite de la formation par simulation.

Measurement of the

The cross section of the ^{13}C(α,n)^{16}O reaction is needed for nuclear astrophysics and applications to a precision of 10% or better, yet inconsistencies among 50 years of experimental studies currently lead to an uncertainty of ≈15%. Using a state-of-the-art neutron detection array, we have performed a high resolution differential cross section study covering a broad energy range. These measurements result in a dramatic improvement in the extrapolation of the cross section to stellar energies potentially reducing the uncertainty to ≈5% and resolving long standing discrepancies in higher energy data.

Telehealth and Transformation of Nursing Care in Saudi Arabia: A Systematic Review.

Introduction: Technological advancements have transformed nursing care, quality, and education across the globe. In the Kingdom of Saudi Arabia (KSA), the inventions and adoption of mobile technologies such as an e-health application (app) called SEHA continue to revolutionize the healthcare system in the country. Purpose: The present systematic review is aimed at examining the technological impact on nursing in Saudi Arabia. The study provides a comprehensive analysis of telehealth and its role in nursing quality, nursing practice, and education. Methods: The present study adopted a literature review methodology by deriving data from journal articles from different databases, for example, Web Science, Google Scholar, CINAHL, MEDLINE, and PubMed databases. Inclusive years for the search ranged from 2016 to 2022. A total of eight articles were found dovetailing to meet the research objectives and answer research questions. Result: After appraising and analyzing the research, the present review found that (Abolfotouh et al., 2019) telehealth in nursing is loosely researched; (Ahmed et al., 2021) telehealth impacts nursing practice and quality by fostering nurse-patient communication promoting positive outcomes, seamless nursing care, and positive experiences; and (Albahri et al., 2021) telehealth and telemedicine is a central tenet of contemporary nursing education and practice. Conclusion: From these findings, this analysis informed three key recommendations: the need to integrate telehealth into the nursing curriculum, telehealth training, and reskilling among healthcare workers (HCWs) in KSA and further primary studies focusing predominantly on telenursing. Overall, telehealth remains a fundamental transformation of nursing practice that forms a central ideology in the contemporary nursing process.

Neutron-upscattering enhancement of the triple-alpha process.

The neutron inelastic scattering of carbon-12, populating the Hoyle state, is a reaction of interest for the triple-alpha process. The inverse process (neutron upscattering) can enhance the Hoyle state's decay rate to the bound states of 12C, effectively increasing the overall triple-alpha reaction rate. The cross section of this reaction is impossible to measure experimentally but has been determined here at astrophysically-relevant energies using detailed balance. Using a highly-collimated monoenergetic beam, here we measure neutrons incident on the Texas Active Target Time Projection Chamber (TexAT TPC) filled with CO2 gas, we measure the 3α-particles (arising from the decay of the Hoyle state following inelastic scattering) and a cross section is extracted. Here we show the neutron-upscattering enhancement is observed to be much smaller than previously expected. The importance of the neutron-upscattering enhancement may therefore not be significant aside from in very particular astrophysical sites (e.g. neutron star mergers).

Assessment of hot flushes and vaginal dryness among obese women undergoing bariatric surgery.

OBJECTIVE: Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of menopausal symptoms such as hot flushes. This assessment will explore whether the prevalence and bother of hot flushes and vaginal dryness change from pre- to post-bariatric surgery among obese midlife women. METHODS: This study is a longitudinal analysis of data from 69 women (ages 35-72 years) undergoing bariatric surgery with reported reproductive histories and menopausal symptoms at preoperative and 6-month postoperative visits. Prevalence of and degree of bother of hot flushes and vaginal dryness at pre- and post-surgery were compared using McNemar's test and Wilcoxon signed-rank test. RESULTS: The reported degree of bother of symptoms associated with hot flushes decreased from pre- to post-surgery (p < 0.01). There was no significant change in the prevalence of hot flushes or vaginal dryness in the overall study sample. CONCLUSIONS: The degree of bother of symptoms associated with hot flushes among midlife women may decrease after bariatric surgery. These results highlight important secondary gains, including less bothersome menopausal symptoms, for women who choose bariatric surgery for weight loss.

Medical strategies for weight loss in the overweight and obese patient.

In recent years, obesity has become a major public health problem in Western countries. The World Health Organization has defined obesity as a global epidemic of the third millennium. Treatment options for weight management include dietary intervention, physical activity, behavior modification, pharmacotherapy and surgery. However, the complexity of this chronic condition necessitates a coordinated multidisciplinary team-approach to the care of obese patients who fail weight control. The long-term duration of the treatment and the necessity of monitoring compliance and effectiveness should be considered. The objective of this article was to review the major controlled randomized clinical trials dealing with the different medical strategies for weight loss and its maintenance in overweight and obese patients.

Repair of ventral hernias in morbidly obese patients undergoing laparoscopic gastric bypass should not be deferred.

BACKGROUND: There is no consensus regarding the optimal treatment of ventral hernias in patients who present for weight loss surgery. METHODS: Medical records of consecutive morbidly obese patients who underwent laparoscopic Roux-en-Y (LRYGB) gastric bypass with a secondary diagnosis of ventral hernia were reviewed. Only patients who were beyond 6 months of follow-up were included. RESULTS: The study population was 85 patients. There were three groups of patients according to the method of repair: primary repair (59), small intestine submucosa (SIS) (12), and deferred treatment (14). Average follow-up was 26 months. There was a 22% recurrence in the primary repair group. There were no recurrences in the SIS group. Five of the patients in the deferred treatment group (37.5%) presented with small bowel obstruction due to incarceration. CONCLUSION: Biomaterial mesh (SIS) repair of ventral hernias concomitant with LRYGB resulted in the most favorable outcome albeit having short follow-up. Concomitant primary repair is associated with a high rate of recurrence. All incarcerated ventral hernias should be repaired concomitant with LRYGB, as deferment may result in small bowel obstruction.

Sealing effect of fibrin glue on the healing of gastrointestinal anastomoses: implications for the endoscopic treatment of leaks.

BACKGROUND: The adoption of advanced laparoscopic techniques for complex surgical procedures has raised the concern that the leak rate might be higher than for open surgery, particularly in the surgeon's early experience or in difficult cases. In this study, the sealing effect of fibrin glue on leaking gastrointestinal anastomoses was evaluated in an experimental swine model. METHODS: A standardized gastrojejunostomy was performed on 20 female pigs (mean weight, 47.7 +/- 5.7 kg). A leak was created on the anterior surface of the anastomosis. The animals were randomized to either fibrin glue or no treatment of the leak. Clinical conditions and vital signs, including body temperature, heart rate and, respiratory rate, were collected three times a day. Preoperative and postoperative complete and differential blood count and lactate dehydrogenase levels were determined. Postmortem analysis was performed when the animals were killed. RESULTS: Clinical signs of peritonitis developed in the control animals by the second or third postoperative day. Findings that confirmed the presence of an anastomotic leak at the postmortem examination were the presence of food or gastrojejunal juices in the abdominal cavity, a localized abscess, or a positive air leak test. Fibrin glue treatment prevented the development of peritonitis in all the animals. Complete sealing of the leak was observed on postoperative day 7 in all treated animals, except one in which an asymptomatic contained leak developed. The postoperative total white blood count was significantly increased in the untreated group (24.69 +/- 5.5 vs 12.74 +/- 3.7 10(3)/ul p < 0.001, paired t-test), as compared with the treated group (15. 55 +/- 2.4 vs 14.89 +/- 2.7 10(3)/ul; p = 0.24). CONCLUSION: In this study, fibrin glue showed reproducible sealing effects on leaking gastrojejunal anastomoses. Fibrin glue application may be a valuable approach for the treatment of gastrointestinal anastomotic leaks.

The learning curve for laparoscopic Roux-en-Y gastric bypass is 100 cases.

BACKGROUND: The purpose of this study was to determine the effect of operative experience on perioperative outcomes for laparoscopic Roux-en-Y gastric bypass (LGB). METHODS: Between July 1997 and September 2001, 750 patients underwent LGB for the treatment of morbid obesity at our center. We evaluated the perioperative outcomes of the first 150 consecutive patients to determine if a learning curve effect could be demonstrated. The patients were divided into three groups (1, 2, and 3) of 50 consecutive patients, and outcomes for each group were compared. RESULTS: The patients in group 3 had a larger body mass index (BMI), were more likely to have had prior abdominal surgery, and were more likely to have secondary operations at the time of LGB. Operating time decreased from a mean of 311 min in group 11 to 237 min in group 3, and technical complications were reduced by 50% after an experience of 100 cases. CONCLUSIONS: Operative time and technically related complications decreased with operative experience even though heavier patients and higher-risk patients were more predominant in the latter part of our experience. LGB is a technically challenging operation with a long learning curve. To minimize morbidity related to the learning curve, strategies for developing training programs must address these challenges.

Bryostatin/ionomycin-activated T cells mediate regression of established tumors.

We have shown that adoptive transfer of tumor-sensitized lymphocytes activated in vitro with bryostatin-1 and ionomycin (B/I), and expanded in culture, can induce regression of small established tumors. We set out to determine whether similar treatment would be effective against larger tumors and what cells mediate this effect. We also attempted to shorten the ex vivo culture period with the ultimate aim of developing a more clinically useful protocol. BALB/c mice were injected in one footpad with IL-2-transfected 4T07 mammary tumor cells. Ten days later, popliteal draining lymph nodes (DLN) were harvested and activated with B/I for 18 h. Mice with either 3-day or 10-day 4T07 flank tumors were treated with cyclophosphamide (100 mg/ kg ip, CYP) alone or CYP followed the next day by infusion of either B/I-activated lymphocytes transferred immediately or activated cells that had been expanded in vitro for 3 or 10 days. In some experiments, mice were also treated with rat anti-mouse CD4 monoclonal antibody (GK1.5) or anti-CD8 antibody (2.43). All mice receiving CYP alone or CYP + sensitized, nonactivated DLN cells demonstrated progressive tumor growth. One hundred percent (6/6) of mice treated with CYP + AIT with B/I-activated,10-day expanded cells had complete regression of 3-day flank tumors. Treatment with activated, nonexpanded cells, induced tumor regression in a majority of mice, but was not as reliable as AIT with expanded cells. We developed a protocol with a shortened expansion period (3-day) that was efficacious for treatment of 4T07 when adoptively transferred to either 3 or 10 day tumor-bearing mice. In vivo depletion of CD4(+) cells had no effect on regression of 3-day tumors, but treatment with anti-CD8 antibody abrogated the effect of immunotherapy. Adoptive transfer of B/I-activated cells, with or without long-term expansion, induced regression of early and late stage 4T07 tumors and is dependent on CD8(+) but not CD4(+) T cells.

Surgical management of gastroesophageal reflux disease in obese patients.

Obesity or morbid obesity is common among patients who are seeking surgery for refractory gastroesophageal reflux disease (GERD). Several surgical options for treating GERD in obese patients are available. Fundoplications may be effective, at least in the short-term, but have no effect on weight loss and comorbidity reduction. Silicone-adjustable gastric banding and Roux-en-Y gastric bypass have different antireflux mechanisms, but also have proven efficacy against GERD and result in significant weight loss and comorbidity reduction. Vertical banded gastroplasty is not an effective antireflux procedure, and it may induce GERD in some patients. The malabsorbtion operations have no proven efficacy against GERD. Patients with severe obesity who are seeking surgical treatment for GERD should be considered for silicone adjustable gastric banding or Roux-en-Y gastric bypass because of the added benefit of weight loss and consequent comorbidity reduction.

Laparoscopic pancreatic necrosectomy.

We describe a patient with infected pancreatic necrosis who was treated successfully with minimally invasive surgery. Five weeks after an episode of acute uncomplicated pancreatitis, he was found to have infected pancreatic necrosis and splenic vein thrombosis. The patient underwent a laparoscopic pancreatic necrosectomy, splenectomy, and cholecystectomy. Seven days after surgery, the patient was discharged and continued to be asymptomatic for the 6 months of follow-up.

Biochemical, hematologic, and immunologic alterations following hepatic cryotherapy.

Hepatic cryosurgery causes hepatocellular damage primarily by inducing the formation of ice crystals. Cell necrosis is enhanced using two or more freeze-thaw cycles. The resultant damage to hepatocytes induces alterations in a number of biochemical and hematologic parameters, including hepatic function tests, serum bilirubin, serum and urine myoglobin, platelet count, and coagulation measures. Further, in experimental models, cryogenic surgery appears to stimulate the immune system of the host leading to an anti-tumor immune response. These perturbations in biochemical and hematologic parameters are usually transient, and long-term adverse sequelae are uncommon and preventable.

Sensitizing T-lymphocytes for adoptive immunotherapy by vaccination with wild-type or cytokine gene-transduced melanoma.

BACKGROUND: For the relatively nonimmunogenic B16-F10 murine melanoma, it has been found that genetically engineered expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not interleukin (IL)-2, IL-4, or interferon-gamma (IFN-gamma) resulted in a vaccine that could induce resistance to rechallenge. Because T cells from lymph nodes draining the sites of some progressive tumors can mediate tumor regression after in vitro activation, it seemed possible that even apparently nonimmunogenic melanoma cells might induce similar preeffector cells in the vaccine-draining lymph nodes (DLNs). METHODS: C57BL/6 mice were vaccinated with B16-F10 cells that were either unmodified or genetically modified to produce IL-2, IL-4, GM-CSF, or IFN-gamma. DLNs were harvested 10 days after vaccination for adoptive immunotherapy (AIT). The DLN cells were activated with bryostatin 1 and ionomycin (B/I), expanded for 10 days in culture, and transferred to mice with 3-day pulmonary metastases. Pulmonary nodules were counted 14 days after AIT. RESULTS: Adoptive transfer of expanded DLN lymphocytes sensitized by inoculation of WT B16-F10, or IL-4, GM-CSF, or IFN-gamma expressing cells significantly reduced pulmonary metastases. Despite the spontaneous regression of IL-2-transduced B16-F10 tumors, DLN from mice inoculated with IL-2 producing B16 cells had little or no antitumor activity. CONCLUSIONS: B16-F10 vaccination strategies that apparently do not induce systemic immunity can effectively sensitize DLN preeffector cells.

Biologic therapy of melanoma with cytokines and lymphocytes.

Melanoma has a somewhat unpredictable behavior, and spontaneous regressions do occasionally occur. Many have surmised that these are the result of immunologic attack by the host. Immunologic treatment has been more successful for melanoma than for most other neoplasms, even with relatively crude therapies, such as bacterial products. With the availability of recombinant cytokines, immunotherapy for melanoma has entered a new era. Interleukin-2 (IL-2), which acts entirely through immunologic mechanisms, has been tested extensively, either alone, in combination with other cytokines, or with adoptive cellular therapy. Alone, it has only modest antitumor activity, even at high doses. Its utility may be greater when combined with immunocompetent cells, especially tumor-sensitized T lymphocytes, in adoptive immunotherapy. On the other hand, nonspecific lymphokine-activated killer (LAK) cells do not appear to add significantly to the efficacy of IL-2 alone. Interferon-alpha (IFN-alpha) [corrected] also has had fairly limited activity in the advanced disease setting, but, on the basis of a recently completed randomized trial, has arguably become the "standard of care" in the adjuvant setting for patients with high-risk melanoma, particularly node-positive patients. A number of regimens combining IL-2, IFN-alpha, and chemotherapeutic agents have yielded striking response rates in small trials and await confirmation in larger studies. With better delineation of the host immune response and definition of relevant tumor antigens, we can look forward to exciting results with combinations of vaccines, cytokines, and adoptive cellular approaches, particularly in patients with micrometastatic disease.

Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration.

Bryostatin 1 activates and subsequently down-regulates protein kinase C (PKC) in vitro and has potential use as an immunomodulator and as an anti-cancer agent. Despite extensive examination of its activities in vitro and anti-tumor effects in vivo, previous studies have failed to document that bryostatin 1 modulates total cellular PKC activity in tumor or normal tissues when administered in vivo. After a single bolus injection of bryostatin 1 (1.0 microgram) in normal C57BI/6 mice, blood was drawn at various intervals and assayed for bryostatin 1 levels. In addition, spleens from bryostatin-treated mice were harvested 10 min to 10 days after treatment, weighed and analyzed for cell numbers, PKC activity and cell surface phenotypes. Bryostatin 1 levels in plasma rose rapidly, reaching peak levels of 56.5 nM less than 1 min after injection, and then declined to undetectable levels by 1 h. A similar pattern was observed when bryostatin 1 was incubated with leukemia cells in vitro, raising the possibility that the rapid fall in plasma levels results from intracellular uptake and binding. Bryostatin 1 induced marked depletion of total splenocyte PKC activity (as much as 69% relative to control values) at 24-96 h after drug administration, but not at earlier times (i.e. 1 h). A single injection of bryostatin 1 also induced expression of the T cell activation marker CD69, leading to positivity in 53% of cells at 3-24 h versus 11% in control mice, and resulted in marked splenomegaly, associated with increased numbers of nucleated cells at 48-96 h. Together, these studies demonstrate that despite rapid disappearance of the drug from plasma, a single i.v. dose of bryostatin 1 exhibits significant and sustained effects on normal murine spleen cells, including early lymphocyte activation, prolonged depletion of PKC activity, splenocyte proliferation and splenomegaly. These findings may have implications for attempts to understand the in vivo effects of bryostatin 1 in normal host tissues.