Low-dose Drug Research Articles

Peritumoral Microgel Reservoir for Long-Term Light-Controlled Triple-Synergistic Treatment of Osteosarcoma with Single Ultra-Low Dose.

Local minimally invasive injection of anticancer therapies is a compelling approach to maximize the utilization of drugs and reduce the systemic adverse drug effects. However, the clinical translation is still hampered by many challenges such as short residence time of therapeutic agents and the difficulty in achieving multi-modulation combination therapy. Herein, mesoporous silica-coated gold nanorods (AuNR@SiO2 ) core-shell nanoparticles are fabricated to facilitate drug loading while rendering them photothermally responsive. Subsequently, AuNR@SiO2 is anchored into a monodisperse photocrosslinkable gelatin (GelMA) microgel through one-step microfluidic technology. Chemotherapeutic drug doxorubicin (DOX) is loaded into AuNR@SiO2 and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is loaded in the microgel layer. The osteosarcoma targeting ligand alendronate is conjugated to AuNR@SiO2 to improve the tumor targeting. The microgel greatly improves the injectability since they can be dispersed in buffer and the injectability and degradability are adjustable by microfluidics during the fabrication. The drug release can, in turn, be modulated by multi-round light-trigger. Importantly, a single super low drug dose (1mg kg-1 DOX with 5mg kg-1 DMXAA) with peritumoral injection generates long-term therapeutic effect and significantly inhibited tumor growth in osteosarcoma bearing mice. Therefore, this nanocomposite@microgel system can act as a peritumoral reservoir for long-term effective osteosarcoma treatment.

Impact of urate-lowering therapy on quality of life indicators in patients with gout

Gout can have a significant impact on the quality of life (QoL) of patients.Objective: to assess the dynamics of QoL indicators and the possibility of achieving the target level of uric acid (UA) in patients with gout on febuxostat therapy, with ineffectiveness and / or contraindications to the allopurinol administration.Patients and methods. The prospective, single-center study included 80 patients with gout. The follow-up period was at least 6 months of allopurinol or febuxostat (Azurix®) therapy in doses required to achieve the target UA level. When urate-lowering therapy was initiated, allopurinol 100 mg per day was prescribed, followed by dose titration (up to maximum of 900 mg per day) until the target UA level was reached (<360 μmol/L). Patients with ineffectiveness of allopurinol and / or adverse reactions (ADRs) were transferred to febuxostat 80–120 mg per day. To prevent arthritis attacks, all patients received low doses of non-steroidal anti-inflammatory drugs or colchicine 0.5 mg per day or glucocorticoids 7,5 mg per day (in prednisolone equivqlent). At the first and last visits, patients on febuxostat completed the SF-36 questionnaire.Results and discussion. After 6 months of follow-up, 70 (88%) patients received urate-lowering therapy, of whom 51 (73%) reached the target UA level. Allopurinol dosage titration required 26 patients, of whom 14 (54%) achieved the treatment goal. Due to the ineffectiveness of allopurinol, 32 patients were switched to febuxostat, which allowed to achieve normouricemia in 69% of cases. Fifteen (68%) of 22 patients who were initiated with febuxostat due to ADRs to allopurinol also achieved the target UA level. Patients who received febuxostat and reached the target UA level improved QoL indicators: role-physical functioning, bodily pain, general health, vitality and general physical well-being (p<0.05 in all cases). Patients who did not reach the target UA level on febuxostat therapy improved such indicators as physical functioning, role-physical functioning, and bodily pain (p<0.05 in all cases). High compliance was observed in 63% of patients, treated with febuxostat and in 36% of patients, treated with allopurinol.Conclusion. In patients with ineffectiveness or intolerance to allopurinol, in 69% of cases febuxostat allows to achieve the target UA level and improving QoL and complience.

Dynamic enzymatic synthesis of γ-cyclodextrin using a photoremovable hydrazone template

Dynamic enzymatic synthesis of γ-cyclodextrin using a photoremovable hydrazone template

A promising chemical series of positive allosteric modulators of the μ-opioid receptor that enhance the antinociceptive efficacy of opioids but not their adverse effects

Positive allosteric modulators (PAMs) of the μ-opioid receptor (MOR) have been proposed to exhibit therapeutic potential by maximizing the analgesic properties of clinically used opioid drugs while limiting their adverse effects or risk of overdose as a result of using lower drug doses. We herein report in vitro and in vivo characterization of two small molecules from a chemical series of MOR PAMs that exhibit: (i) MOR PAM activity and receptor subtype selectivity in vitro, (ii) a differential potentiation of the antinociceptive effect of oxycodone, morphine, and methadone in mouse models of pain that roughly correlates with in vitro activity, and (iii) a lack of potentiation of adverse effects associated with opioid administration, such as somatic withdrawal, respiratory depression, and analgesic tolerance. This series of MOR PAMs holds promise for the development of adjuncts to opioid therapy to mitigate against overdose and opioid use disorders.

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

PurposeTraditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery.MethodsWet-sieving and spray-congealing were employed as innovative techniques to evaluate the impact of engineering on the particle properties of D-mannitol. To that end, the resulting powders were characterized concerning their solid-state, micromeritics and flowability. Afterwards, the engineered carrier particles were blended with inhalable size beclomethasone dipropionate to form low dose (1 wt%) DPI formulations. The in vitro aerosolization performance was evaluated using the NEXThaler®, a reservoir multi-dose device.ResultsWet-sieving generated D-mannitol particles with a narrow particle size distribution and spray-congealing free-flowing spherical particles. The more uniform pumice particles with deep voids and clefts of wet-sieved D-mannitol (Pearl300_WS) were beneficial to drug aerosolization, only when used in combination with a ternary agent (10 wt% of ‘Preblend’). When compared to the starting material, the spray-congealed D-mannitol has shown to be promising in terms of the relative increase of the fine particle fraction of the drug (around 100%), when used without the addition of ternary agents.ConclusionsThe wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose.

Effects of a combined treatment regimen consisting of Hsp90 inhibitor DS-2248 and radiation in vitro and in a tumor mouse model

BackgroundHeat shock protein 90 (HSP90) is a molecular chaperone that is responsible for the conformational maintenance of several client proteins that play important roles in DNA damage repair, apoptosis following radiation, and resistance to radiation therapy. DS-2248 (tricyclic pyrazolopyrimidine derivative) is a newly-developed, orally available inhibitor of HSP90 with low adverse effects. We investigated the combined effects of radiation and DS-2248 in vitro and in vivo.MethodsSCCVII squamous cell carcinoma cells and tumors transplanted in C3H/HeN mice were used. In vitro combined effects of X-ray radiation and DS-2248 were investigated using a colony assay. Phosphorylated histone H2AX (γH2AX) was quantified after 2-Gy irradiation with or without 24-hour pretreatment with DS-2248. The mice bearing SCCVII tumors received oral DS-2248 10 times over 2 weeks and received local irradiation with doses of 1, 2, 3, and 4 Gy delivered 6 times over 2 weeks. Then, tumor volumes were measured.ResultsRadiation plus pretreatment with 50 nM DS-2248 for 24 hours produced synergistic effects on SCCVII cells. γH2AX foci persisted after radiation for longer periods (6 and 24 hours) in DS-2248-treated cells than in control cells. In vivo, the combined effects appeared to be additive when 5 or 10 mg/kg DS-2248 was combined with total radiation doses of 6–18 Gy, but the effect was considered supra-additive when 15 mg/kg of DS-2248 was combined with a total dose of 24 Gy.ConclusionsThe combined effects of DS-2248 and radiation were additive at low drug and radiation doses, but may have been supra-additive at higher doses. Inhibition of slow repair of DNA double strand breaks (i.e., homologous recombination) was considered to contribute to this combined effect.

Preliminary results of the efficacy and safety of all-trans retinoic acid combined with low-dose apatinib in the treatment of patients with recurrent/metastatic adenoid cystic carcinoma of the head and neck.

6026 Background: There is no standard treatment for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). Moreover, MYB and/or NOTCH1 mutation can lead to worse prognosis. Currently, anti-angiogenic targeted therapy is a relatively effective treatment option, but the accompanied toxicities may hinder the continuous medication. All-trans retinoic acid (ATRA) induces differentiation and promotes apoptosis, enhancing the cytotoxicity of anti-tumor agents; on the other hand, inhibits c-MYB and/or NOTCH1 expression. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We reported the preliminary results of the efficacy and safety of ATRA combined with low-dose apatinib in patients with R/M ACC. Methods: In this exploratory study, patients with pathologically or histologically confirmed advanced, R/M ACC with measurable disease were screened. Patients who previously received anti-angiogenic therapy then withdrew due to toxicities could be recruited. ATRA was administered orally at a dose of 20 mg twice a day, and apatinib was administered orally at a dose of 250 mg once a day. The primary endpoint was objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors v1.1. Results: Between March 2019 and April 2020, a total of 16 patients were enrolled. The median age was 53 years (range: 35-69), and 7 (44%) patients were male. Four (25%) patients received ATRA plus apatinib as the third-line therapy, while 12 (75%) received as the second-line therapy. Of 16 patients, 3 (19%) achieved partial response and 13 (81%) achieved stable disease (SD), with ORR of 19% and disease control rate of 100%, respectively. Among patients with SD, 12 (75%) showed tumor shrinkage (3%-28%) and 1 (6%) showed minor tumor enlargement (2%). The median follow-up time was 14.5 months (range: 8.1-22.1). Throughout the period, 5 (42%) patients developed disease progression. The 6-month and 12-month progression-free survival rates were 100% and 80%, respectively. Grade 3 adverse events included hand-foot syndrome (1 [6%]) and proteinuria (1 [6%]). No grade ≥4 adverse events occurred. Conclusions: ATRA combined with low-dose anti-angiogenic drug apatinib could be a potential treatment option for patients with R/M ACC, including those with pretreated advanced ACC after progression on or intolerance to other therapies. These encouraging results were worth further investigations, and a randomized phase 2 trial in ongoing (the Aplus study, NCT04433169).

The need for publicly funded research on therapeutic use of psychedelic drugs.

The need for publicly funded research on therapeutic use of psychedelic drugs.

Polarization of Tumor-Associated Macrophages by Nanoparticle-Loaded Escherichia coli Combined with Immunogenic Cell Death for Cancer Immunotherapy.

The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Herein, tumor-associated macrophage polarization therapy supplemented with PLGA-DOX (PDOX)-induced ICD is developed for cancer treatment. The nanoparticles/bacteria complex (Ec-PR848) is fabricated for tumor targeting and TAM polarization, and PLGA-R848 (PR848) are attached to the surface of Escherichia coli (E. coli) MG1655 via electrostatic absorption. The toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and E. coli can greatly polarize M2 macrophages to M1 macrophages, while PDOX-induced ICD can also impair the immunosuppression of the tumor microenvironment. This strategy shows that tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapeutic drugs can commendably enhance the efficacy of immunotherapy.

A COMPARATIVE STUDY OF TWO DIFFERENT LOW DOSES OF HYPERBARIC 0.5% BUPIVACAINE IN SADDLE ANAESTHESIA FOR DAY CARE SURGERIES

This study was done to compare the hospital stay and side effects of two low doses of bupivacaine plus buprenorphine in saddle block for day care surgeries in patients admitted in shri aurobindo institute of medical sciences indore. Low dose of bupivacaine drug in saddle anesthesia allows rapid onset and early patient mobilization and a short stay in hospital particularly in day care surgeries.(1 )Several studies targeting local anaesthetic at specic nerve roots supplying the surgical eld have demonstrated successful results.(2 )We compare the efcacy and early discharge of patients given low dose of 4.5mg bupivacaine for saddle blockade in perianal procedures compared with the dose 5.5mg bupivacaine, both with 30ug buprenorphine in addition for post operative analgesia.(3) Descriptive and inferential statistical analyses were performed using SPSSversion20.0 software.

Evaluation of the preliminary clinical effect of flap-raising combined with cortical-perforation technique in tooth extraction cases of patients with potential risk of medication-related osteonecrosis of the jaw

Objective: To evaluate the preliminary clinical effect of flap-raising and cortical-perforation based extraction method in patients with potential risk of medication-related osteonecrosis of the jaw (MRONJ). Methods: Eighteen patients, who needed teeth extraction in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from February 2016 to November 2020, with a history of using anti-resorption/anti-angiogenesis medication were included in this retrospective study. According to the characteristics of the patient's medication history, patients were stratified into three categories, low-dose anti-resorption drug group, high-dose anti-resorption drug group, and high-dose anti-resorption combined with anti-angiogenesis targeted drug group. There were 15 females and 3 males, the average age was 62.4 years (range from 27 to 87 years) old. A total of 31 teeth were indicated for extraction due to chronic infection. The flap-raising and cortical-perforation techniques were used to extract the affected teeth, and the patients were followed up closely. By observing the healing status and swelling degree of the mucosa of tooth extraction sites, whether there was a fistula, pus and bone exposure of jaw bone,the healing of the tooth extraction sites were evaluated. Results: Among the 18 patients, there were 9 cases of osteoporosis and 9 cases of malignant tumors. Classified by medication-using history, 10 cases were treated with low-dose anti-resorption drugs, 5 cases were high-dose anti-resorption drugs, and 3 cases were high-dose anti-resorption drugs combined with anti-angiogenesis drugs. A total of 31 teeth of the patients were extracted by flap-raising and cortical-perforation based extraction method. Thirteen patients completed treatment underwent local anesthesia and five cases were performed under general anesthesia. The shortest follow-up period was 3 months with an average of 13.2 months. Seventeen patients recovered well after the tooth extraction. One patient had the mandible exposed at one extraction site one month after the surgery, resulting in MRONJ. Conclusions: In patients with potential risks of MRONJ, the application of flap-raising and cortical-perforation based teeth extraction method could safely and effectively alleviate the dental inflammation in the oral cavity.

Producing High-Dose Liqui-Tablet (Ketoprofen 100 mg) for Enhanced Drug Release Using Novel Liqui-Mass Technology

PurposeLiqui-Tablet is a dosage form derived from Liqui-Mass technology. It has proven to be a promising approach to improve drug dissolution rate of poorly water-soluble drugs. So far, Liqui-Tablet is feasible for low-dose drugs. In this study, an attempt was made to produce high-dose Liqui-Tablet, whilst maintaining ideal physicochemical properties for ease of manufacturing.MethodsLiqui-Tablets containing 100 mg of ketoprofen were produced using various liquid vehicles including PEG 200, Span 80, Kolliphor EL, PG, and Tween 85. Investigations that were carried out included saturation solubility test, dissolution test, tomographic study, and typical quality control tests for assessing flowability, particle size distribution, friability, and tablet hardness.ResultsThe weight of these Liqui-Tablets was acceptable for swallowing (483.8 mg), and the saturation solubility test showed PEG 200 to be the most suitable liquid vehicle (493 mg/mL). Tests investigating physicochemical properties such as flowability, particle size distribution, friability, and tablet hardness have shown no issue concerning quality control and manufacturability. The drug release test of the best formulation has shown extremely rapid drug release at pH 7.4 (100% after 5 min). At pH 1.2 the drug release was reasonable considering the formulation was yet to be optimized.ConclusionDespite the high amount of API and liquid vehicle, it is possible to produce a high-dose dosage form with acceptable size and weight for swallowing using the novel Liqui-Mass technology. This has the potential to diversify the technology by removing the restriction of high dose drug that has been seen in liquisolid technology.

The effect of preoperative sublingual buprenorphine on postoperative pain after lumbar discectomy: A randomized controlled trial

BackgroundLumbar discectomy is one of the most common surgical procedures performed to manage pain caused by the protrusion of an intervertebral disc. Postoperative pain management can be challenging and might lead to increased intake of opioids. Objective: The aim of this study was to determine the effect of preoperative sublingual buprenorphine on severity of pain after lumbar disc surgery and postoperative intake of morphine. MethodsThis Randomized clinical trial study was performed on 78 patients who were selected for lumbar discectomy surgery. Patients were randomly divided into two groups of 39 patients, each. Patients in the buprenorphine and placebo group received 2 mg buprenorphine sublingual, and placebo 1 h before surgery. Severity of pain, nausea, vomiting and pruritus and intake of opioids in the two groups were evaluated and recorded 1, 6, 12 and 24 h after surgery. Data were analyzed using SPSSv21. ResultsThere was a significant difference in pain score in buprenorphine group at 1, 6, 12, and compared with placebo (P < 0.005). In the control group, the use of analgesics was more than the buprenorphine group. In the first hours after surgery (1–6 h), the incidence of nausea in the buprenorphine group was significantly lower than of the control group (P < 0.05). However, at 12 and 24 h, this difference was not observed, p > 0.05. There was no significant difference in incidence of side effects (nausea, vomiting, pruritus) in the two groups (P > 0.05). ConclusionSublingual buprenorphine in postoperative pain management is an effective and low dose drug. Due to its simpler administration, it is recommended to relief postoperative pain after lumbar disc surgery.

CEREBRALANEURYSM SURGERY IN A PATIENT WITH CHRONIC RENAL FAILURE: PERIOPERATIVE CONCERNS AND CONFLICTS

Chronic renal failure (CRF) and associated multi-system abnormalities can adversely impact the outcome in patients undergoing high-risk aneurysm surgeries by causing hemodynamic instability, uid-electrolyte imbalance, bleeding and coagulation abnormalities, decreased anesthetic drug excretion, and dialysis-related complications. Conicts between the standard perioperative practices in aneurysm surgery and those in CRF further contribute to the management challenges. These include, using low anesthetic drug doses but achieving good brain relaxation, using a restrictive uid therapy but preventing postoperative vasospasm, and avoiding diuretics causing nephrotoxicity but reducing intracranial pressure. Ayoung male with dialysis-dependent CRF and hypertension underwent emergency craniotomy and clipping of a cerebral aneurysm. He was managed with a modied protocol of reduced heparin hemodialysis, BIS-guided use of minimum anesthetic drugs, goal-directed optimum uid therapy, maintaining hemodynamic stability, and management of post-aneurysm clipping vasospasm with hypertension. His perioperative management and related conicts are discussed

Frequency of ABCB1 C3435T and CYP3A5*3 Genetic Polymorphisms in the Lebanese Population.

CYP3A5 and ABCB1 are highly implicated in the pharmacokinetics and pharmacodynamics of immunosuppressive agents, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. The polymorphisms of their coding genes play important roles in the interindividual and intraindividual differences of bioavailability of these drugs. In this study, our objective was to investigate, in a Lebanese population,the frequency of ABCB1C3435T (rs1045642) and CYP3A5*3 (rs776746) polymorphisms and to compare the results to preexisting data from other populations. We determined the frequencies of the allelic variants of interest for 1824 Lebanese participants, and we compared these results with those from other major ethnic groups. The allelic frequencies were 91.4% (C) and 8.6% (T) for CYP3A5*3 and 50.8% (T) and 49.2% (C) for ABCB1 C3435T. Our results were significantly different from most other world populations, except the European population. The frequencies of gene variants of interest in our Lebanese population were similar to those found in European populations. Most of our study population were CYP3A5*3 carriers, and more than half may have a lower P-glycoprotein efflux pump. These characteristics might render Lebanese transplant recipients more prone to the development of drug toxicity and in need of lower drug doses.

Tamarindus indica. Linn leaves ameliorates experimental induced heart failure in Wistar rats

Cardiovascular diseases (CVDs) are highly prevalent in various countries, and heart failure accounts for the majority of deaths. The present study focuses on determining the protective effect of ethanol extract of leaves of Tamarindus indica (TIEE) by in vitro and in vivo methods. In vitro cardiotonic activity was determined using Langendorff's heart perfusion assembly. In vivo studies were performed using Doxorubicin (1.5mg/kg, i.p for sevendays) induced cardiotoxicity in rats. These animals were simultaneously treated with the TIEE at a low dose (200mg/kg, p.o), high dose (400mg/kg, p.o) and standard drug Digoxin (100μg/kg, p.o) for sevendays. At the end of the study, various parameters like electrocardiogram (ECG) recording, serum levels of serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and presence of cardiac troponin (cTnI) were determined. Isolated hearts were subjected to histopathological studies. The TIEE at a concentration of 60μg/mL showed a significant cardiotonic effect in vitro that was evident by increased force of contraction, heart rate, and cardiac output. In vivo studies revealed that the TIEE decreased the prolongation of QT and RR interval of ECG, lowered the serum enzyme levels like LDH, CPK indicating cardiac protection, and the same was established by the absence of cTnI in blood. Histopathological examinations of heart tissue sections showed improved architecture in the treatment groups when compared with diseased groups. The study revealed the cardioprotective activity of T.indica leaf extract by both in vitro and in vivo methods.

Effect of preprocedural pharmacologic cardioversion on pulmonary vein isolation in patients with persistent atrial fibrillation.

The optimal strategy for catheter ablation of persistent atrial fibrillation (PeAF) remains unknown. A preprocedural additive treatment for patients undergoing pulmonary vein isolation (PVI) alone to optimize catheter ablation should be investigated. The purpose of this study was to determine whether pharmacologic cardioversion with a fixed low-dose antiarrhythmic drug (AAD) before ablation could stratify the long-term outcome of a PVI-alone strategy. We conducted a prospective cohort study of PeAF patients who underwent PVI using contact force-sensing catheters. No substrate modification was performed. Fixed low-dose bepridil was administered before ablation for cardioversion and patients were classified into 2 groups based on obtaining sinus rhythm (SR). The rate of recurrence of atrial fibrillation (AF) and/or atrial tachycardia (AT) within 36 months was compared between the 2 groups. Among the 303 PeAF patients who received the AAD, 102 returned to SR (SR group), and the other 201 had persistence of AF (non-SR group). AF persistence duration at baseline and during bepridil administration was similar between the 2 groups. The SR group had a significantly lower 36-month AF/AT recurrence rate than the non-SR group (17 [22.2%] vs 55 [34.0%], log-rank P = .022). AT-type recurrence was observed in 16 patients (2 [3.3%] in the SR group vs 14 [8.9%] in the non-SR group; log-rank P = .051). Nonresponse to AAD was an independent predictor of AF/AT recurrence after adjusting for other risk factors (hazard ratio 1.34; 95% confidence interval 1.01-1.77; P = .040). Preprocedural pharmacologic cardioversion could be a useful determinant for patients with treatable PeAF by PVI alone.

Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death

ABSTRACT While treatments for colorectal cancer continue to improve, some 50% of patients succumb within 5 years, pointing to the need for additional therapeutic options. We have developed a modified non-replicating adenoviral vector for gene transfer, called AdRGD-PG, which offers improved levels of transduction and transgene expression. Here, we employ the p53-responsive PG promoter to drive expression of p53 or human interferon-β (hIFNβ) in human colorectal cancer cell lines HCT116wt (wtp53), HCT116−/- (p53 deficient) and HT29 (mutant p53). The HCT116 cell lines were both easily killed with p53 gene transfer, while combined p53 and hIFNβ cooperated for the induction of HT29 cell death and emission of immunogenic cell death (ICD) markers. Elevated annexinV staining and caspase 3/7 activity point to cell death by a mechanism consistent with apoptosis. P53 gene transfer alone or in combination with hIFNβ sensitized all cell lines to chemotherapy, permitting the application of low drug doses while still achieving significant loss of viability. While endogenous p53 status was not sufficient to predict response to treatment, combined p53 and hIFNβ provided an additive effect in HT29 cells. We propose that this approach may prove effective for the treatment of colorectal cancer, permitting the use of limited drug doses.

Pharmacotherapy for borderline personality disorder: A review

IntroductionBorderline personality disorder (BPD) is characterized by instability of interpersonal relationships, self-image, and emotions, and by impulsivity. Although patients with BPD are misdiagnosed, some of them receive mental health treatment. Even if the first-line treatment of this disorder is psycotherapy, the patients with BPD may be highly symptomatic and are often prescribed multiple medications in a manner unsupported by evidence.ObjectivesThe aim of this study is to study the available evidence about the pharmacotherapy for borderline personality disorder.MethodsA review of the available literature about the management of borderline personality disorder and de pharmacotherapy for personality disorders was performed.ResultsFirst-line treatment of the personality disorders is psycotherapy. The treatment plan for BPD may include individual and group therapy, medication, self-education, specialized substance use disorder treatment, partial hospitalization, or brief hospitalization during times of crises. Medications are generaly used only as adjuncts to psychotherapy and the adjunctive use of symptom targeted medications has been found to be useful. There is limited information to guide pharmacotherapy; preliminary evidence limits the practice of polypharmacy. Sympton-domain focused medication treatment is recommeded by some guidelines: cognitive-perceptual symtoms (low-dose antipsychotic drugs), impulsive-behavioral dyscontrol (mood stabilizers), affective dysregulation (mood stabilizers and low-dose antipsychotic drugs) and self-harm (omega-3 fatty acids).ConclusionsBPD cause significant distress and impariment of social, occupational and role functioning. The first-line treatment for BPD is psychotherapy; however symptom-focused, medication treatment of BPD is generally considered to be an adjunct to psychotherapy. The data support the efficacy of low dose antipsychotic drugs and mood stabilizers.

Rosacea — modern features of pathogenesis and the possibility of drug correction in the era of growing antibiotic resistance

The pathophysiology of rosacea is a complex process in which the following factors are important: vascular disorders, changes in the connective tissue of the dermis, microorganisms, dysfunction of the gastrointestinal tract, immune disorders, changes in the sebaceous hair apparatus, oxidative stress, climatic factors, psycho-vegetative disorders, constitutional angiopathy, emotional stress, hormonal imbalance, exposure to chemical agents. Therapy for rosacea can be difficult for specialists and cause patient dissatisfaction due to a recurrent course. The treatment of severe forms of the disease is especially difficult. Traditional antibiotic therapy and correction of hormonal levels in women give a positive, but often temporary effect. Objective — to study the efficacy and tolerability of systemic isotretinoin in the treatment of papulopustular forms of rosacea. Materials and methods. The study involved 30 patients (21 women and 9 men) aged 39 to 56 years who had papulopustular rosacea. Evaluation of the effectiveness of therapy was carried out using the scale of diagnostic assessment of rosacea before and after 6 months from the start of treatment. All patients were prescribed systemic isotretinoin as monotherapy — the drug Roaccutane (F. Hoffmann-La Roche Ltd, Switzerland) in the following dose: during the 1st month — 0.3 mg/kg, during the 2th—6th months — 0.2 mg/kg once a day along with fatty foods. Results and dicsussion. Before treatment, the rosacea diagnostic scale score was (10.8 ± 0.9) points. After 6 months of therapy, it decreased 6 times and equaled to (1.8 ± 0.4) points. Conclusions. The analysis of the data obtained indicates a high efficiency of Roaccutane in the treatment of papulopustular forms of rosacea. Side effects in the form of dry skin and mucous membranes when taking Roaccutane were minor due to the low dose of the drug and were corrected with appropriate moisturizers.