Adjuvant

Background and Aims: Supraclavicular brachial plexus block is frequently used procedure to provide anaesthesia and good post-operative analgesia for surgery on upper limb. The purpose of this study was to compare the hemodynamic, sedative and analgesic effects of ropivacaine alone versus ropivacaine given along with dexmedetomidine.
Materials and Methodology: This prospective, randomized and double-blinded study included total 60 patients of either sex with age between 18-60 years posted for various elective upper limb surgery and randomly allocated into 2 equal groups of 30 each. Control Group-R received injection ropivacaine (0.75%) 30 ml plus 1 ml normal saline and Group-RD received injection ropivacaine (0.75%) 30 ml plus dexmedetomidine 25 μg (1 ml) for supraclavicular brachial plexus block using the peripheral nerve stimulator. Sensory and motor block, monitoring of vitals (systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)), presence of any side effect, Ramsay sedation score and visual analogue scale or visual analog scale (VAS) score were determined every 5 mins in 1st 30 mins and then every 15 mins during 1st hr followed by every 2nd hourly during 24 hrs.
Results: There was no significant difference in the study groups with regards to demographic profile and duration of surgery. The onset of sensory and motor blockade was faster in Group-RD than Group-R. {Onset of sensory block: (Group-R=14.133±1.676 min and Group-RD=12.667± 1.213 min) (p=0.000), Onset of motor block: (Group-R=25.967±2.748 min and Group-RD=23.333±3.467 min) (p=0.002). Also total duration of sensory blockade {Group-R=547.833±26.152 mins, Group-RD=811.667±25.405 mins (p value=0.000)}, motor blockade {Group-R=509.667±24.703 mins, Group-RD=760.667±28.062 mins (p value=0.000)} and number of rescue injections in 24 hrs {Group-R=2.733±0.450, Group-RD=1.400±0.498 (p value=0.000)} was significantly different in 2 groups. There was good haemodynamic stability in both groups. SBP and DBP in Group-R and Group-RD with p values 0.416 and 0.784 were comparable between the groups. The difference was statistically not significant. There was no incidence of any side effects like hypotension and bradycardia in any of the 60 patients.
Conclusion: Dexmedetomidine in a dose of 25 μg added to ropivacaine in supraclavicular brachial block for upper limb surgery significantly shortens the onset time and prolongs the duration of sensory and motor block without producing sedation in patients.

Immunomodulators are natural or synthetic materials that regulate the immune system and induce innate and adaptive defense mechanisms. These substances are classified into two types, immunostimulants and immunosuppressants. Immunostimulants can enhance body's resistance against various infections through increasing the basal levels of immune response. These agents could increase the oxidative activity of neutrophils, augment engulfment activity of phagocytic cells, and stimulate cytotoxic cells as necessary defense mechanisms. Many disorders could be treated using some immunostimulants such as autoimmune diseases, viral infections, and cancer. The researchers classified the immunostimulants using their origin and mode of action such as bacterial products, complex carbohydrates, vaccines (antigens and adjuvants), cytokines, immunoenhancing drugs, nutritional factors, animal extracts, and plant extracts. In this mini-review, the concepts, types, and functions of immunostimulants will be described as a therapeutic approach against different diseases.

Peste des petits ruminants (PPR) virus belongs to the family Paramyxoviridae and represents a major threat to small livestock industry. In recent years, outbreaks of PPR have occurred in Turkey and North Africa. In endemic areas, disease prevention is accomplished using live‑attenuated vaccines. However, the use of live vaccines in non‑endemic regions, such as Europe, is not approved by Veterinary Authorities. In these regions inactivated vaccines are then the only viable alternative. In this study an inactivated vaccine (iPPRVac) was formulated with either a water‑in‑oil emulsion (ISA 71 VG) or with delta inulin adjuvant, alone (AFSA1) or combined with a TLR9 agonist oligonucleotide (AFSA2). These formulations were then tested for immunogenicity on rats. The iPPRV formulation with AFSA2 adjuvant induced 100% seroconversion in rats after 2 injections and was subsequently evaluated in goats. Five goats were immunised twice subcutaneously, 36 days apart with iPPRVac + AFSA2. The immunised goats all seroconverted to PPR by day 9 and remained seropositive until the end of the experimental period (133 days). These data indicate that the rat model is useful in predicting vaccine responses in goats and that inactivated vaccine, when formulated with a delta inulin adjuvant, represents a promising alternative to live attenuated vaccines for PPR vaccination campaigns in non‑endemic areas.

With the onset of antigen creation utilizing biosynthetic and rDNA strategies, the need to manage adjuvants alongside immunizations has expanded astoundingly. This quest for going with adjuvants has brought about a large number of atoms from mineral salts to bacterial polysaccharides and Immuno stimulatory edifices that extent significantly in viability. In addition, the adjuvant particle is particular to its antigen atom and henceforth must be custom-made appropriately to boost adequacy and security, keeping up the expense at the very least. This paper investigates the attributes of these particles, their method of activity and the headways in the field.

Bempegaldesleukin (BEMPEG: NKTR-214) is an immunostimulatory IL-2 cytokine prodrug engineered to deliver a controlled, sustained and preferential IL-2 pathway signal. Nivolumab (NIVO), a PD-L1 inhibitor, has been shown to prolong survival in patients with advanced melanoma and recurrence-free survival in the adjuvant setting. PIVOT-02 showed that BEMPEG plus NIVO was well-tolerated and demonstrated clinical activity as first-line therapy in metastatic melanoma. PIVOT-12 is a randomized, Phase III, global, multicenter, open-label study comparing adjuvant therapy with BEMPEG plus NIVO versus NIVO alone in adult and adolescent patients with completely resected cutaneous stage III/IV melanoma at high risk of recurrence. The primary objective is to compare the efficacy, as measured by recurrence-free survival, of BEMPEG plus NIVO versus NIVO.

Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oi...

The restimulation of an immune memory response by in vitro culture of blood cells with a specific antigen has been used as a way to gauge immunity to vaccines for decades. In this commentary we discuss a less appreciated application to support vaccine process development. We report that human whole blood from pre-primed subjects can generate a profound adjuvant-modulated, antigen-specific response to several different vaccine formulations. The response is able to differentiate subtle changes in the quality of an immune memory response to vaccine formulations and can be used to select optimal conditions relating to a particular manufacture process step. Whilst questions relating to closeness to in vivo vaccination remain, the approach is another big step nearer to the more relevant human response. It has special importance for new adjuvant development, complementing other preclinical in vivo and in vitro approaches to considerably de-risk progression of novel vaccines prior to and th...

Among the many potential benefits arising from the rapidly advancing field of nanomedicine is the possibility of a whole new range of nanovaccines in which novel delivery mechanisms utilizing nanoparticles could make obsolete the use of needles for administering any vaccine. However, as the massive resources of the worldwide pharmaceutical industry are deployed to develop nanovaccines, urgent questions arise as to which diseases should be targeted and which populations will benefit most. This paper explores how such targeting of nanovaccines might be decided in an ethically optimal way and considers some of the practical considerations and potential problems of implementing such a global nanovaccine policy. There seems little doubt that nanomedical research could develop vaccines against most major global infectious diseases. Throughout the history of medicine, however, it is well recognized that insufficient attention and resources have been given to public health and preventive me...

To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin(®) SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Background and Aim: The Aujeszky's disease, also known as Pseudorabies, remains one of the most problematic fulminant diseases in domestic animals, affecting the central nervous system. The study aimed to investigate the effect of an inactivated vaccine against Aujeszky's disease based on "Kordai" virus strain.

Materials and Methods: To test the inactivation of the "Kordai" strain (grown by the roller method in VNK-21/13 cell culture with an infectious titer of at least 7.5 lg TCD50/ml) which is causative of Aujeszky's disease, next-generation teotropin and propolis preparations were used in concentrations of 0.1%, 0.08%, and 0.04%.

Results: As a result of comparative studies on the optimization of parameters for inactivating the "Kordai" virus strain, it was established that teotropin is a more effective inactivant than propolis. At the same time, the optimal final concentration of teotropin for inactivation was 0.1%, along with a reaction medium temperature of 37°C, pH of 7.4-7.6, and duration of inactivation of 14 h. The titer of virus-neutralizing activity (VNA) of antibodies at the pH (neutralization reactions) in vaccinated sheep of 10-12 months of age was 7.5±0.3, Ig TCID50/ml (tissue culture infectious dose 50%), and 3.5±0.3 in the cell culture VNK-21/13 (culture of Syrian hamster kidney cells).

Conclusion: To determine colostral immunity in newborn lambs, the method of metabolic status correction was used to vaccinate lambs obtained from immune sheep 4 months after birth. The results showed that lambs obtained from immune sheep had high VNA titers. A sustained immune response in vaccinated animals was obtained after double vaccination.

Humans have turned to natural products, obtained from plants, animals and aquatic life for treating diseases since time immemorial. Modern medicine is based on ancient wisdom transferred over generations. Drug development relies mainly on natural sources. Herbal medicines are making a comeback due to lower side effects, and positive results in the long term when compared to synthetic drugs. The current drug discovery process relies on identifying traditional medicines followed by Bioactivity-guided fractionation to isolate significant lead molecules. Plants have a history of long-term use by humans and hence it can be presumed that the bioactive compounds obtained from plants will have low human toxicity. There exists a huge potential for discovering new antitumor drug leads by screening natural products either in the form of crude extracts purified phytochemicals which have already been described in the literature. The fact that phytochemicals like paclitaxel, vinblastine, vincrist...