31 Flavonoids sterols, triterpenoids, alkaloids and phenolics are known to be bioactive antidiabetic

principles. 32 Flavonoids are known to regenerate the damaged beta cells in the alloxan induced diabetic rats. 33 Phenolics are found to be effective antihyperglycemic agents. On this basis we have selected the glucose induced hyperglycaemic model to screen the anti-hyperglycaemic activity of the plant extracts. Liver function tests (LFTs) are commonly used in clinical practice to screen for liver disease, monitor the progression of known disease, and monitor the effects of potentially hepatotoxic drugs. The most common LFTs include the serum aminotransferases, alkaline phosphatase, bilirubin. Hepatocellular damage causes release of these enzymes into circulation. Increase Selleckchem Talazoparib in

serum levels of AST shows hepatic injuries similar to viral hepatitis, infarction, and muscular damages. ALT, which mediates conversion of alanine to pyruvate and glutamate, is specific for liver and is a suitable indicator of hepatic injuries.34 In the present study, the level of SGOT, SGPT and bilirubin level were significantly increased.35 Increased level of serum marker enzymes due to directly conversion small molecule library screening of amino acids to keto acids are AST and ALT. Inflammatory hepatocellular disorders results in extremely elevated transaminase levels.36 The increase in the activities of plasma AST and ALT indicated that diabetes may be induced hepatic dysfunction. Supporting our findings it has been found by Larcan et al.37 that liver was necrotized in diabetic

patients. Chronic Ketanserin mild elevation of amino transferase is frequently found in type 2 diabetic patients. Therefore, an increase in the activities of AST and ALT in plasma may be mainly due to the leakage of these enzymes from the liver cytosol into the blood stream.38 Further that, our results on the recovery after treatment with S. cumini seed extract are in parity with findings with other plants reported by other workers. 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 and 41 In conclusion, the present study demonstrated that the treatment of diabetic mice with S. cumini has exerted a considerable hypoglycemic effect. In addition, these herbs could be liver damage associated with alloxan diabetes. However, further biochemical studies should be conducted to promote using of these herbs as antidiabetic agents. All authors have none to declare. Authors are thankful to Director, Mahavir Cancer Sansthan & Research Centre, Patna, Bihar (India) for providing required facilities for the current study. We also thank Head of the Department for providing the animals for the present work. “
“Thorax innovation (TORINO) Marc Humbert, Le Kremlin-Bicêtre, France Drugs induced pulmonary arterial hypertension Andrei Seferian et al., Le Kremlin-Bicêtre, France Complications of chemotherapy, a basic science update Marianne Mazevet et al.

Cell suspensions from the different tissues of individual mice (n = 3 mice per group for each timepoint) were gated on live cells (based on forward and side scatter plots) and positive and negative gates were set using cell suspensions from equivalent tissues collected from mice injected with unlabelled pDNA ( Fig. 5A, top panel). We observed a few pDNA-Cy5+ cells in peripheral blood, but none were detected in spleen or bone marrow at this timepoint. This result suggested that some pDNA rapidly enters the peripheral blood from the injection site. Fluorescence microscopy of popliteal lymph nodes showed labelled

DNA in the subcapsular sinus and throughout paracortical areas (data not shown), as has been described previously [19], suggesting that injected pDNA drains into the proximal lymph nodes via the afferent

lymphatic vessels. In all cases, cell suspensions from unlabelled pDNA-immunised mice showed very little background staining (<0.04%). At 24 h we found pDNA-Cy5-containing Natural Product Library cells in draining (popLN and ILN) and ABT199 distal peripheral lymph nodes ( Fig. 5A, bottom panel). As observed for the 1 h timepoint, the popliteal LN contained the highest percentage of positive cells (∼0.4% live cells). Although we were unable to find cell-associated pDNA in the peripheral blood at 24 h, we were able to demonstrate positive cells in both the spleen and bone marrow at this timepoint. In other experiments, we attempted to characterise the cells associated with pDNA-Cy5 using multicolour flow cytometry. Analysis of draining and distal LNs and spleen at 24 h indicated that they were CD45/Ly5+ (haematopoietic), MHC Class MTMR9 II+, CD11b+ and mostly B220−, although a few B220+ cells were also associated with pDNA-Cy5 (Fig. 5B and Table 1). pDNA was rarely found in CD11chigh cells, suggesting that monocytic cells, possibly macrophages or immature monocytes (CD11b+, CD11c−) are the predominant cell type initially associated with pDNA following intramuscular DNA injection. Too few pDNA-Cy5+

cells were found in peripheral blood to phenotype. pDNA in bone marrow was restricted to CD45/Ly5+, CD11b+, MHC Class II−, which is suggestive of an immature myeloid/monocyte cell phenotype. Data presented from one experiment (n = 3 per group) shows that the percentage of pDNA-Cy5+ cells is statistically increased in both popliteal LN and spleen at 24 h ( Fig. 5C). The percentage is increased in 2 out of 3 mice in the BM but does not reach statistical significance. In summary, pDNA is cell-associated in LNs draining the injection, in more distal LNs, in peripheral blood, spleen and BM, thus suggesting that pDNA is widely disseminated following intramuscular injection and hence there are multiple pathways for pDNA to reach secondary lymphoid tissue. We (this study), and others [1], have observed pMHC-bearing cells in peripheral lymph nodes soon after a single immunisation of soluble protein Ag, with large numbers of CD11c+ cells bearing pMHC complexes at 24 h post-injection.

g. increasing condom use or reducing partner numbers); (ii) increased screening, treatment buy Tenofovir and contact tracing/partner notification; (iii) the development of new biomedical prevention or therapeutic technologies (such as vaccines) (see review by Gottlieb et al. in this issue) [15]. However, it is not feasible to implement behaviour change campaigns to a sufficient scale and efficacy to result in population-level impacts.

Since a Chlamydia vaccine is not currently available, the only viable public health strategy is the scale-up of screening for chlamydial infection coupled with the administration of a course of antibiotics and counselling or follow up for partner notification or contact tracing and also rescreening. Chlamydia screening may be cost-effective and partner notification is an effective adjunct, with treatment using azithromycin evaluated to be cost-effective [16].

Screening is generally considered to be acceptable and feasible among most target populations [17] and [18]. However, uptake is likely to be the limiting factor, ABT-199 cost even in ideal study conditions with specific invitations for screening, with less than 45% of populations at risk of Chlamydia being routinely screened [18], [19], [20], [21] and [22]. Modelling studies have indicated that at least 45–60% screening levels are required to have noticeable epidemiological impacts [22], [23], [24] and [25] and these coverage levels, or greater, must be sustained at least annually, indefinitely. It is

unlikely Resminostat that the coverage and frequency of screening and treatment interventions could reach sufficiently high levels to result in epidemic declines approaching elimination. Not only are there issues of limited coverage and frequency which reduces effectiveness, but treatment efficacy is not perfect [26], [27] and [28], drug resistance is possible, re-infection is extremely common, [29] and [30] and there is no end to the need to continue regular rescreening. In addition, despite continued improvements in diagnostic and screening procedures for Chlamydia, and although antibiotics like azithromycin are available to treat infections, notifications of infections continues to increase. Antibiotic treatment of individuals may also increase susceptibility to re-infection, which is most likely due to interrupting the natural course of protective chlamydial immunity [31]. Recently, data from an in vivo study reported that not only were T-helper (Th)1 immune responses against C. trachomatis in individual women slow to develop, but that these responses were also altered by treatment with ceftriaxone and azithromycin [32]. Taken together, these facts suggest that the current main line of defence against chlamydial infections (i.e.

Interestingly, PD0332991 increases in alpha-1 receptor stimulation in PFC also occur during traumatic brain injury (Kobori et al., 2011), which is known to be a risk factor for PTSD (Bryant, 2011). Thus alpha-1 receptors are a rational therapeutic target for treating PTSD. The high levels of catecholamine release during acute stress not only impair PFC function, but strengthen amygdala function, switching control of behavior to more primitive circuits. There are feedforward

interactions that set up “vicious vs. delicious cycles” to maintain the orchestration of brain circuits in fundamentally different states. As shown in Fig. 1, there is a “Delicious cycle” during nonstress conditions where moderate levels of phasic NE release engage high affinity alpha-2A receptors which strengthen PFC (see above), weaken amygdala (DeBock et al., 2003), and normalize tonic firing of LC neurons (Svensson et al., 1975 and Nestler et al., 1999) and NE release (Engberg and Eriksson, 1991). This enhances PFC function, providing intelligent regulation of the LC and amygdala. Thus, these interactive mechanisms maintain a state that promotes top-down regulation of brain and behavior. In contrast, stress exposure rapidly switches brain orchestration of behavior to primitive circuits, as summarized in Fig. 2. Stress activates feed-forward vicious cycles whereby the amygdala activates the LC and VTA to increase catecholamine release

(Goldstein et al., 1996 and Valentino et al., 1998), which in turn takes PFC “off-line” through alpha-1 receptor activation. Loss of PFC Trametinib function further erodes regulatory control of the amygdala, striatum and brainstem (Arnsten, 2009), while the high levels of catecholamine release strengthen amygdala function via alpha-1AR, beta-AR and DA receptors

(Ferry et al., 1999 and Nader and LeDoux, 1999). Increased amygdala activity continues to drive the LC, thus maintaining the vicious cycle. Higher catecholamine levels have been linked to PFC impairments during stress in humans as well (Qin et al., 2012), suggesting that these mechanisms holds across species. With sustained stress, there are both chemical of and architectural changes that exacerbate the effects of stress on brain function. The mechanisms underlying spine loss are just beginning to be understood, with data suggesting that inhibiting alpha-1-protein kinase C signaling (Hains et al., 2009), stimulating alpha-2A receptors (unpublished data), or promoting growth factors such as FGF-2 (Elsayed et al., 2012) can protect PFC spines from sustained stress exposure. There are also alterations in the catecholamine systems themselves with prolonged stress exposure. Studies in rodents suggest that the DA system depletes with chronic stress (Mizoguchi et al., 2000), while the NE system is strengthened. Most studies show that chronic stress increases the tonic and/or evoked firing of LC neurons (Nestler et al.

MMC and EMC showed antibacterial activity against S. aureus (28 mm, 15 mm), B. subtilis (23 mm, 20 mm), K. pneumonia (12 mm, 15 mm), P. vulgaris (22 mm, 27 mm) and E. coli (28 mm, 20 mm) at 100 μg concentration itself and increased activity with increasing concentrations. PF-06463922 nmr This effect was concentration-dependent. It doesn’t produce any effect in 50 μg, whereas, both the extracts do not inhibit the fungi, A. niger and C. albicans. The present study involved in pharmacognostical characterization of M. cochinchinensis seeds to confirm the taxa and to avoid the substitutes in indigenous medicinal preparations. The

staining results were remarkably good and some cytochemical reactions were also obtained. Comparative anatomical studies on seeds of Mucuna Adans and Canavalia DC. species were studied and resolved that the features such as rim-aril, cuticle, palisade layer of osteosclereids, macrosclereids, Doxorubicin mouse hour glass cells, mesophylls and tracheid – bar of M. pruriens and other six species are common, but anatomical structures at hilar region seems to be important for diagnostic purpose. 9 Our results coincides the characterization results described earlier and thereby confirmed the species selected. Disc diffusion methods are used extensively to investigate the antibacterial activity of natural substances and plant extracts. Antibacterial

property of methanolic seed extracts of M. pruriens has been very well demonstrated. 10 and 11 Methanol extract of leaf of M. pruriens shows strong antibacterial activity against S. aureus, B. subtilis, E. coli and P. aeruginosa. 12 In this study MMC and EMC produced remarkable

antibacterial efficacy when compared with standard drug Chloramphenicol. Phytochemical analysis revealed the presence of flavonoids in both the extracts. Flavonoids Resminostat have been used extensively since centuries for the treatment of various diseases. 13 Quercetin, naringenin are reported to inhibit B. subtilis, C. albicans, E. coli, Staphylococcus nervous, Staphylococcus epidermis and Saccharomyces cerevisiae. 14Psidium guajava leaves are reported to have morin-3-O-lyxoside, morin-3-O-arabinoside, quercetin, quercetin-3-O-arabinoside and all these four possess bacteriostatic action against all food borne pathogenic bacteria including Bacillus stearothermophilus, Brochothrix thermosphacta, E. coli, Listeria monocytogenes, Pseudomonas fluorescens, Salmonella enteric, S. aureus, Vibrio cholera. 15 Flavonones having sugar moiety also exhibit potent antimicrobial activity. 16 The activity demonstrated here may be due to the presence of flavonoids in MMC and EMC. The pharmacognostic investigation shows that authentic botany of this crude drug prevents adulteration, substitution and has a crucial role in standardization of crude drugs. The preliminary phytochemical screening of the seeds of M. cochinchinensis indicates the presence of secondary metabolites, having an essential role in medicine.

Mycobacterial HSP65, which has about 50% homology with the human homologue HSP60 [38] serve as the carrier for the diabetogenic peptide P277, may interact with B cells. Recent studies show that HSPs enhance delivery and cross-processing of HSP-linked Ag by B cells [35] and [39]. Although the effects of antigen presentation by various antigen-presenting cells to cloned CD4+ T cells in vitro has not been tested in the present study, the idea has been

established that dendritic cells and macrophages promote antigen-specific Th1 cell differentiation, and B cell presentation of antigen usually induces T cell anergy and tends to promote naïve T cell differentiation toward an anti-inflammatory Th2 phenotype [40], [41], [42] and [43]. Interestingly, T cells from the HSP65-6 × P277 treated mice when incubated with P277 the pattern of cytokine showed an increase in IL-10 and a decrease in IFN-γ (Fig. 4). If activated P277-specific B cells this website serve as APCs and present HSP65-6 × P277 to T cells, it might be promote antigen-specific

Screening Library ic50 Th2 cell differentiation. Moreover, the capacity of Th2 cells to function as T-helper cells for antibody production is severely hampered in the control mice, which recruited lower levels of P277-specific B cells than HSP65-6 × P277 treated mice (Fig. 1). It is conceivable that the absence of P277-specific B cells to act as antigen-presenting cells may be responsible, in part at least, for the decrease of Th2 cell differentiation in the HSP65 and P277 treated mice. In this study, the mice immunization with the fusion protein HSP65-6 × P277 elicited much higher levels of Th2-type cytokines and lower Th1-type cytokines than the control mice (P < 0.05). A possible explanation for the enhanced Th2-regulated immune response in HSP65-6 × P277 treated mice is that when P277-specific B cells are recruited, the dramatic increase in levels of IL-4 or other Th2-type cytokines. This occurs by the modulation of

the homing of autoreactive cells to inflammatory sites and the stabilization of a protective Th2-mediated environment in the pancreatic islets ( Fig. 2 and Fig. 3). Thus, IL-4 favors the expansion of regulatory CD4+ Th2 cells in vivo that would normally be subject to promote retention of the Th2 phenotype. The respiratory tract is a less acidic the and proteolytic environment and it has been an attractive route of immunization. Nasal administration of autoantigen decrease organ-specific inflammation has been tested experimentally in several models of autoimmunity. For example, nasal administration of HSP65 in mice lacking the receptor for LDL can cause significant decrease in the size of atherosclerotic plaques, and suppress inflammation and atherosclerosis development [16]. Weiner HL et al showed that nasal administration of amyloid A-β peptide limits decreased amyloid plaque deposition in a transgenic animal model of Alzheimer’s disease [44].

8%) had glaucoma in both eyes. Seventeen of all included patients (2.9%) were registered in the administration system of the Habilitation and Assistive Technology Service

only. Median time between last visit and death was 8 months BI 2536 solubility dmso (interquartile range 3-16 months). Median age at death was 87 years (range 50-103 years). There were 423 patients in the Data at Diagnosis group (71.5%). In those patients mean age at diagnosis was 74.0 ± 7.9 years, ranging from 46-95 years. Exfoliative glaucoma was found in at least 1 eye in 170 patients (40.2%). Average perimetric MD at diagnosis was −5.59 ± 5.69 dB and −11.83 ± 8.18 dB in the better and the worse eye, respectively. Median VA at time of diagnosis was 0.8 (20/25), ranging from no light perception to 1.00 (20/20), in the perimetrically better eye and 0.8 (20/25), ranging from no light perception to 1.25 (20/16), in the perimetrically JQ1 in vitro worse eye. Untreated mean intraocular pressure (IOP) value in all glaucomatous eyes at time of diagnosis was 27.2 ± 8.8 mm Hg. Numbers of patients with low vision and blindness from glaucoma at the last visit are shown in the Table. At the last visit, 42.2% (250 of 592 patients) of all patients were blind from glaucoma in at least 1 eye and 16.4% in both eyes. Other reasons for unilateral blindness

were age-related macular degeneration (AMD) (26 patients), a combination of cataract and other disease (10 patients), and other causes (32 patients). Seventeen patients were bilaterally blind because of reasons other than glaucoma (16 from AMD, 1 patient from other reason). A

combination of causes for blindness was found in 1 eye of 7 blind patients (Table). There was no statistically significant difference in the frequencies Astemizole of visual impairment at the last visit when comparing the Data at Diagnosis group and the Follow-up Only group (Table, P = .260). In patients who developed blindness attributable to glaucoma, the median time with bilateral blindness was 2 years (<1-13) (mean 3.0 ± 3.1). Patients who became bilaterally blind from glaucoma did so at a median age of 86 years (range 66-98; mean 85.7 ± 6.1). Only 13 patients (13.5% of blind patients and 2.2% of all patients) became blind before the age of 80 years. The median duration with diagnosed glaucoma was 12 years (<1-29) (mean 11.2 ± 6.6), and 74.7% (316 of 423 patients) of patients had their glaucoma diagnosis for more than 6 years. The cumulative incidence for blindness in at least 1 eye and bilateral blindness from glaucoma was 26.5% and 5.5%, respectively, at 10 years and 38.1% and 13.5%, respectively, at 20 years after diagnosis (Figure 3, Top left and Bottom left). The corresponding cumulative incidences for blindness caused by other reason were 0.7% and 0.7%, respectively, at 10 years and 2.4% and 2.6%, respectively, at 20 years (Figure 3, Top left and Bottom left). The Kaplan-Meier estimates for blindness in at least 1 eye caused by glaucoma were 33.1% at 10 years and 73.

The physiotherapist and participant discussed and documented whether they felt any selleck chemicals exacerbation was related to neural tissue management or to some other change in activity level. Neural tissue management was stopped

if an exacerbation occurred that was associated with the development of two or more abnormal neurological findings. The participant was monitored after the follow-up assessment and referred for medical management as necessary. Data were retained for statistical analysis in accordance with intention-to-treat principles (Moher et al 2010). Participants assigned to the control group received only advice to continue their usual activities. This provided a measure of the natural

history of nerve-related neck and arm pain. To encourage these participants to remain in the study for the 4-week control period without treatment, they were advised that they would receive treatment afterwards, as shown in Figure 1. After the trial, they received four complimentary treatments from one of the trial’s physiotherapists. Interventions were at the physiotherapists’ discretion and no data were collected. The primary outcome for the benefits of neural tissue management was participant-reported improvement on a 15-point Global Rating of Change scale. The scale spans from –7 (‘a very great deal worse’) to 0 (‘no BIBW2992 change’) to +7 (‘a very great deal better’) (Jaeschke et al 1989). Participants who reported a change ≥+4 (at least ‘moderately better’) at follow-up were classified as ‘improved’. This represents at least moderate improvement in the participant’s condition (Jaeschke et al 1989). Secondary outcomes for the benefits of neural tissue management were improvements in impairments in neck and arm pain intensity and below reduced participant-reported activity limitations. Neck and arm pain intensity were measured by mean numeric pain rating scores for the participant’s current, highest, and lowest levels

of pain during the previous 24 hours (Cleland et al 2008). Participant-reported activity limitations were measured by the Neck Disability Index (Vernon and Moir 1991) and the Patient-Specific Functional Scale (Westaway et al 1998). The Global Rating of Change was also the primary outcome for harms related to neural tissue management. Participants with a change ≤–2 (at least ‘a little worse’) at follow-up were classified as ‘worse’. Secondary outcomes included the number of participants who stopped neural tissue management early because they developed two or more abnormal neurological signs during an exacerbation that they and the physiotherapist related to neural tissue management and adverse events that participants related to neural tissue management.

The Kv-channel inhibition reported here may contribute to the hypertensive effect of MK801 as in the case of ketamine. MK801 is experimentally a potent anticonvulsant and has great potential for use in research for generating animal models of schizophrenia. Unlike dopaminergic agonists that mimic only the positive symptoms of schizophrenia, a single injection of MK801 was successful in modeling both the positive and negative symptoms of schizophrenia (11). Not only has temporary treatment with MK801 been shown to mimic psychosis, but chronic administration of the drug in laboratory animals has also been demonstrated to result in similar Doxorubicin datasheet neuropathological changes as in schizophrenia (35). For MK801-induced

psychosis or schizophrenia, a mechanism generally accepted is the inhibition of the NMDAr

channel or the hypo-glutaminergic theory (5) and (36). However, the interaction of PCP derivatives (such as MK801 and ketamine) and serotonin 5-HT2A receptor or dopamine D2 receptor has also been reported (37), (38), (39), (40) and (41). These reports Hydroxychloroquine suggested that ketamine and PCP may act as agonists (or allosteric activators) of the 5-HT2A and D2 receptors, and that the 5-HT2A and D2 receptors are thus associated with the schizophrenia induced by PCP derivatives. Recently, it was also reported that the discriminative stimulus effect of ketamine involves the 5-HT2A receptor (42). Both in the CNS and peripheral cardiovascular system, signaling of the 5-HT2A receptor involves a decrease of Kv-channel conductance (22),

(28), (43) and (44). Because Kv-channel subunits such as Kv1.5 function as key mediators of 5-HT2A receptor activation, we speculate that MK801 potentiates signaling by the 5-HT2A receptor by inhibiting Kv1.5 (44) and (45). Supporting this notion, in our preliminary experiments, ketamine and MK801 selectively potentiated 5-HT2A receptor-mediated vasoconstriction without affecting adrenergic receptor-mediated vasoconstriction, not especially at the physiological nanomolar concentration ranges of serotonin and norepinephrine (unpublished observation). Moreover, we also observed that MK801 blocked the rat brain Kv1.5 (rKv1.5) channels heterologously expressed in Chinese hamster ovary (CHO) cells (unpublished observation). Based on these results, we suggest that whether Kv-channel inhibition contributes to MK801 effects such as schizophrenia and hypertension should be carefully considered. The hypothesis is schematically illustrated in Supplementary Fig. 2. In the present study, IC50 of MK801 on the Kv channel was around 100 μM. This was surely much higher than the reported plasma level of MK801: it was reported to be ∼0.2 μM in the psychosis rat model (10). However, the drug concentration of specific area in the brain can be much higher than the average blood concentration (46). Moreover, just a small inhibition of Kv channels may induce large alterations in cellular excitability.

He noted that the support from government

is very important to facilitate negotiations with multinationals. The public immunization policy, the population acceptance and the market size are also components of success. A. Homma encouraged DCVMN members to intensify ALK inhibitor cancer discussions and build up closer cooperation and technology transfer initiatives among Network members, which will leverage investments and better prepare emerging manufacturers to meet the supply challenges of developing countries. C. Campa from Finlay (Cuba) noted that the five conditions for Finlay to turn challenges into opportunities included: the support from the local government, the high qualified human resources, the cooperation with other institutions inside and outside the country, confidence and loyalty to the solidarity principles of vaccination programmes

across national borders, and existence of a robust system to carry out clinical trials. S. Gao from Innovax (China) noted that the vaccine manufacturing quality management system is crucial to achieve WHO PQ, rather than the technology itself. He highlighted www.selleckchem.com/products/Dasatinib.html the recombinant vaccines based on a new E. coli expression system as an efficient vaccine technology platform. In addition to Hepatitis E, a new HPV vaccine has been developed based on the expression system. He emphasized that products with high cost-effectiveness will be very important for expanding immunization in developing countries. Finally, he expressed his interest in cooperation with other DCVMN members for technology transfer or development. K. Ella, from Bharat Biotech (India) shared his vision on new vaccines’ development. The attention to the specific health needs of the country and the strong will to be part of a solution to saving the lives of children are the key

to succeed. With support from donors vaccine companies still have to face the challenge of how to keep the quality while keep affordable prices. As illustrated by D. Dat, from Vabiotech (Vietnam), the manufacturers in Vietnam have been working closely with the government since the 1950s to eradicate polio and protect people from other infectious disease. However, applying for WHO PQ is a challenge that keeps the products of Vabiotech away from other populations in the world. Thus the company cooperated with other companies through technology transfer, Linifanib (ABT-869) for cholera vaccines for example, to make the product available globally. M. Datla from Biological E (India) considers quality issues as daily business and great opportunities to introspect and improve the quality management system. She noted that the management of suppliers is also crucial to ensure the quality of final products. As for the partnership with international organizations such as GAVI, M. Datla noted that transparency in relationship and enough patience are very important approaches, especially to recognize the tangible added value of the partners. M.