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1.
Atorvastatin calcium (ATC), an anti-lipid BCS class II drug, is marketed in crystalline and amorphous solid forms. The objective
of this study was to perform solid state characterization of commercial crystalline and amorphous ATC drug samples available
in the Indian market. Six samples each of crystalline and amorphous ATC were characterized using X-ray powder diffractometry
(XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis, Karl Fisher titrimetry, microscopy (hot stage
microscopy, scanning electron microscopy), contact angle, and intrinsic dissolution rate (IDR). All crystalline ATC samples
were found to be stable form I, however one sample possessed polymorphic impurity, evidenced in XRPD and DSC analysis. Amongst
the amorphous ATC samples, XRPD demonstrated five samples to be amorphous ‘form 27’, while, one matched amorphous ‘form 23’.
Thermal behavior of amorphous ATC samples was compared to amorphous ATC generated by melt quenching in DSC. ATC was found
to be an excellent glass former with Tg/Tm of 0.95. Residual crystallinity was detected in two of the amorphous samples by complementary use of conventional and modulated
DSC techniques. The wettability and IDR of all amorphous samples was found to be higher than the crystalline samples. In conclusion,
commercial ATC samples exhibited diverse solid state behavior that can impact the performance and stability of the dosage
forms. 相似文献
2.
The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein
formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs.
β-Glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl
phosphatylcholine:cholesterol (7∶3) was selected as the liposome composition. The lyophilization of liposomes, micronization
of the powders, aerosolization using a dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon collection
in a twinstage liquid impinger were evaluated. After lyophilization and jet-milling, the total amount of GUS and its activity,
representing encapsulation efficiency and stability, were evaluated. The GUS amount and activity were measured and compared
with freshly-prepared liposomes in the presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after lyophilization
and 36% of GUS amount, 22% of activity after micronization were obtained. Emitted doses from dry powder inhaler were 53%,
58%, 66%, and 73% for liposome powder:mannitol carrier ratios of 1∶0, 1∶4, 1∶9, and 1∶19. Fifteen percent of the liposome
particles were less than 6.4 μm in aerodynamic diameter. The results demonstrate that milled liposome powders containing protein
molecules can be aerosolized effectively at a fixed flow rate. Influences of different cryoprotectants on lyophilization of
protein liposome formulations are reported. The feasibility of using liposomal dry powder aerosols for protein delivery has
been demonstrated but further optimization is required in the context of specific therapeutic proteins.
Published: December 21, 2005 相似文献
3.
Complexation of celecoxib with hydroxypropyl β-cyclodextrin (HPβCD) in the presence and absence of 3 hydrophilic polymers—polyvinyl
pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)—was investigated with an objective
of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPβCD and on the dissolution
rate of celecoxib from the HPβCD complexes. The phase solubility studies indicated the formation of celecoxib-HPβCD inclusion
complexes at a 1∶1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were
quite stable. Addition of hydrophilic polymers markedly enhanced the complexation and solubilizing efficiencies of HPβCD.
Solid inclusion complexes of celecoxib-HPβCD were prepared in 1∶1 and 1∶2 ratios by the kneading method, with and without
the addition of hydrophilic polymers. The solubility and dissolution rate of celecoxib were significantly improved by complexation
with HPβCD. The celecoxib-HPβCD (1∶2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of celecoxib.
The addition of hydrophilic polymers also markedly enhanced the dissolution rate of celecoxib from HPβCD complexes: a 72.60-,
61.25-, and 39.15-fold increase was observed with PVP, HPMC, and PEG, respectively. Differential scanning calorimetry and
X-ray diffractometry indicated stronger drug amorphization and entrapment in HPβCD because of the combined action of HPβCD
and the hydrophilic polymers.
Published: September 29, 2006 相似文献
4.
5.
The objective of this work is physicochemical characterization of nimesulide-cyclodextrin binary systems both in solution
and solid state and to improve the dissolution properties of nimesulide (N) via complexation with α-, β, and γ-cyclodextrins
(CDs). Detection of inclusion complexation was done in solution by means of phase solubility analysis, mass spectrometry,
and 1H nuclear magnetic resonance (1H-NMR) spectroscopic studies, and in solid state using differential scanning calorimetry (DSC), powder x-ray diffractometry
(X-RD), scanning electron microscopy (SEM), and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H-NMR studies in solution revealed 1∶1 M complexation of N with all CDs. A true inclusion of N with β-CD at 1∶2 M in solid
state was confirmed by DSC, powder X-RD and SEM studies. Dissolution properties of N-CD binary systems were superior when
compared to pure N. 相似文献
6.
Airaksinen S Karjalainen M Kivikero N Westermarck S Shevchenko A Rantanen J Yliruusi J 《AAPS PharmSciTech》2005,6(2):E311-E322
Phase transformations in formulations can lead to instability in physicochemical, biopharmaceutical, and processing properties
of products. The influences of formulation design on the optimal dosage forms should be specified. The aim here was to investigate
whether excipients with different water sorption behavior affect hydrate formation of nitrofurantoin in wet masses. Nitrofurantoin
anhydrate was used as a hydrate-forming model drug, and 4 excipients with different water-absorbing potential (amorphous low-substituted
hydroxypropylcellulose, modified maize starch, partially amorphous silicified microcrystalline cellulose, and crystalline
α-lactose monohydrate) were granulated with varying amounts of purified water. Off-line evaluation of wet masses containing
nitrofurantoin anhydrate and excipient (1∶1) was performed using an X-ray powder diffractometer (XRPD) and near-infrared spectroscopy,
and drying phase was evaluated by variable temperature XRPD. Only amorphous excipient in the formulation retarded hydrate
formation of an active pharmaceutical ingredient (API) at high water contents. Hygroscopic partially crystalline excipient
hindered hydrate formation of API at low water contents. Crystalline excipient was unable to control hydrate formation of
API. The character of excipient affects the stability of formulation. Thus, correct selection of excipients for the formulation
can control processing-induced phase transitions and improve the storage stability of the final dosage form.
Published: October 6, 2005 相似文献
7.
This study explored the potential of β-cyclodextrin to improve the aqueous solubility and dissolution of danazol, investigated
a simple and less expensive method for preparation of a danazol-β-cyclodextrin binary system, and explored the potential application
of a danazol-β-cyclodextrin binary system as a single-dose emergency contraceptive. Phase solubility analysis indicated formation
of a first-order soluble complex with stability constant 972.03 M−1, while Job's plot affirmed 1∶1 stoichiometry. The hyperchromic shift in the UV-Vis spectrum of danazol in the presence of
β-cyclodextrin indicated solubilization capability of β-cyclodextrin for danazol. The extrinsic Cotton effect with a negative
peak at 280.7 nm confirmed the inclusion of danazol in the asymmetric locus of β-cyclodextrin.1H-nuclear magnetic resonance analysis suggested that the protons of the steroidal skeleton of danazol display favorable interactions
with the β-cyclodextrin cavity. The danazol-β-cyclodextrin binary system was prepared by kneading, solution, freeze-drying,
and milling methods. The extent of the enhancement of dissolution rate was found to be dependent on the preparation method.
Dissolution studies showed a similar relative dissolution rate (2.85) of the danazol-β-cyclodextrin binary system prepared
by the freeze-drying and milling (in the presence of 13% moisture) methods. In a mouse model, the danazol-β-cyclodextrin binary
system at 51.2 mg/kg (equivalent to a 400-mg human dose) showed 100% inhibition of implantation when given postcoitally. Moreover,
the danazol-β-cyclodextrin binary system is safe up to 2000 mg/kg in the mouse (15.52 g/70 kg human) as a single oral dose.
Thus, the danazol-β-cyclodextrin binary system could serve as a new therapeutic application: an oral emergency contraceptive
at a physiologically acceptable single dose.
Published: May 11, 2007 相似文献
8.
Summary A rapid exchange procedure using ammonium acetate as an extractant was developed for measurement of cation exchange capacity
(CEC) of plant roots. The CEC values obtained with 1∶100 and 1∶200 root/solution ratios were almost equal, though the values
increased with length of the time of immersion in both the root/solution ratios. The method gave higher CEC values with fresh
roots as compared to dried roots. However, dried milled and dried unmilled roots gave identical values. 相似文献
9.
Gjertrud Maurstad Marcus Prass Louise C. Serpell Pawel Sikorski 《European biophysics journal : EBJ》2009,38(8):1135-1140
Atomic force microscopy was used to investigate the stability of dehydrated amyloid fibrils formed by human islet polypeptide
(IAPP) and Aβ(1–42) peptides. IAPP amyloid fibrils were imaged in liquid (hydrated state) and in air (dehydrated). In addition,
fibrils dried on the mica surface were rehydrated and re-examined both in liquid and in air (after consecutive redrying).
As reported previously, the initial drying process does not result in any major change in the amyloid appearance and the dimensions
of the fibrils are preserved. However, when once-dried samples are rehydrated, fibril stability is lost. The fibrils disintegrate
into small particles that are attached to the mica surface. This process is further confirmed by studies of the rehydrated
samples after drying, on which the morphology of the fibrils is clearly changed. Similar behavior is observed for Aβ(1–42)
amyloid fibrils, which are apparently stable on first drying, but disintegrate on rehydration. The observed change indicates
that dehydration is causing a change in the internal structure of the amyloid fibrils. This has important implications for
studies of amyloid fibrils by other techniques. Due to the potential influence of hydration and sample history on amyloid
structure, preparation and study of amyloid samples with controlled humidity requires more consideration. 相似文献
10.
Betulinic acid (BA), a novel natural product with antimelanoma activity, has poor aqueous solubility (<0.1 μg/mL) and therefore exhibits poor bioavailability. The purpose of this study was to explore the feasibility of preparing BA solid dispersions (BA-SDs) with hydrophilic polymers to enhance the aqueous solubility of BA. Melt-quenched solid dispersions (MQ-SDs) of BA were prepared at various ratios with the hydrophilic polymers including Soluplus, HPMCAS-HF, Kollidon VA64, Kollidon K90, and Eudragit RLPO. BA was found to be miscible in all polymers at a 1:4 (w/w) ratio by modulated differential scanning calorimetry (MDSC). BA/Soluplus MQ-SD exhibited the highest solubility in simulated body fluids followed by BA/Kollidon VA64 MQ-SD. The MQ-SDs of BA/Soluplus, BA/HPMCAS-HF, and BA/Kollidon VA64 were found to be amorphous as indicated by X-ray powder diffraction (XRPD) studies. Fourier transform infra-red (FT-IR) studies indicated molecular interactions between BA and Soluplus. Our preliminary screening of polymers indicates that Soluplus and Kollidon VA64 exhibit the greatest potential to form BA-SDs.
Electronic supplementary material
The online version of this article (doi:10.1208/s12249-014-0220-x) contains supplementary material, which is available to authorized users.KEY WORDS: betulinic acid, DSC, FT-IR, HPLC, SEM, solid dispersions, solubility, XRPD 相似文献11.
Conclusion An inclusion complex of rofecoxib and HPβ-CD was prepared successfully by the spray-drying method in a molar ratio of 1∶1.
The inclusion complex was found to have improved in vitro drug release compared with the pure drug. The solubility profile
of complexes of rofecoxib prepared using HPβ-CD as the complexing agent in a molar ratio of 1∶1 by the spray-drying method
in pH 1.2 and pH 7.4 indicated that the acid solubility of rofecoxib was enhanced considerably by formation of an inclusion
complex with HPβ-CD. The above results also clearly demonstrated a significant decrease in the gastric ulcerogenic activity
of rofecoxib through complexation with cyclodextrins. Even though the physical mixture of rofecoxib with cyclodextrins reduced
ulcer formation, it was the spray-dried complex formation approach that minimized gastric ulceration. These findings are extremely
important from a commercial point of view as the prepared complex removes a major drawback for rofecoxib in therapy.
Published: September 20, 2005 相似文献
12.
The objective of this work was to develop tablet formulations of nimesulide-β-cyclodextrin (NI-β-CD) and meloxicam-γ-cyclodextrin
(ME-γ-CD) binary systems. In the case of nimesulide, 3 types of binary systems—physical mixtures, kneaded systems, and coevaporated
systems—were studied. In the case of meloxicam, 2 types of binary systems—physical mixtures and kneaded systems—were investigated.
Both drug-CD binary systems were prepared at 1∶1 and 1∶2 molar ratio (1∶1M and 1∶2M) and used in formulation studies. The
tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed
superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall,
the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets
prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration
time, hardness, and in vitro dissolution properties over 6 months at 40°C±2°C and 75% relative humidity.
Published: May 11, 2007 相似文献
13.
The β-casein (CN) human milk fraction is comprised of a single protein phosphorylated at levels from 0 to 5. Component interactions
are dependent on the phosphorylation level. Here, 3 mg/ml of β-CN-0P, β-CN-2P, β-CN-4P, a 2P/4P 1:1 (wt:wt) mixture, or a
mixture of all six forms in the ratio in human milk, were mixed with bovine κ-CN at a κ/β molar ratio of 0.33. Measurements
were with 0, 5 and 10 mM Ca+2 and 4 and 8 mM added inorganic phosphate (Pi). The turbidity (OD400 nm) and a lack of precipitation as T increased from 4 to 37°C was an index of micelle formation. The results indicate: (1) while micelles will form with Ca+2 alone, added Pi has a significant enhancing effect on micelle formation; (2) the patterns of micelle formation as a function of T are influenced by the β-CN-0P and β-CN-1P forms of β-CN to an unexpected extent. 相似文献
14.
The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone
(PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation,
characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and
tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of
the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed
by solid state analyses. Complete drug amorphiztion was attained at 1∶3 (wt/wt) drug: PVP, 25% (wt/wt) ND in PVP. According
to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris
at ∼129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution
efficiency, respectively. In vivo experiments in mice demonstrated that administration of 60 mg/kg of drug coprecipitated
with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure
drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of
ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power,
dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing
a reduced-dose, fast-release solid oral dosage form of nimesulide.
Published: August 10, 2007 相似文献
15.
The aim of this work was to study the influence of β-cyclodextrin (β-CD) on the biopharmaceutic properties of diclofenac (DCF).
To this purpose the physicochemical characterization of diclofenac-β-cyclodextrin binary systems was performed both in solution
and solid state. Solid phase characterization was performed using differential scanning calorimetry (DSC), powder x-ray diffractometry
(XRD), and Fourier transform infrared spectroscopy (FTIR). Phase solubility analyses, and in vitro permeation experiments
through a synthetic membrane were performed in solution. Moreover, DCF/β-CD interactions were studied in DMSO by1H nuclear magnetic resonance (NMR) spectroscopy. The effects of different preparation methods and drug-to-β-CD molar ratios
were also evaluated. Phase solubility studies revealed 1∶1 M complexation of DCF when the freeze-drying method was used for
the preparation of the binary system. The true inclusion for the freeze-dried binary system was confirmed by1H NMR spectroscopy, DSC, powder XRD, and IR studies. The dissolution study revealed that the drug dissolution rate was improved
by the presence of CDs and the highest and promptest release was obtained with the freeze-dried binary system. Diffusion experiments
through a silicone membrane showed that DCF diffusion was higher from the saturated drug solution (control) than the freeze-dried
inclusion complexes, prepared using different DCF-β-CD molar ratios. However, the presence of the inclusion complex was able
to stabilize the system giving rise to a more regular diffusion profile.
Published: October 22, 2005 相似文献
16.
B. J. O. Efiuvwevwere L. G. M. Gorris E. J. Smid E. P. W. Kets 《Applied microbiology and biotechnology》1999,51(1):100-104
Survival of Lactococcus lactis subjected to different drying conditions was investigated. Mannitol most remarkably enhanced the survival of dried cells
to a level almost equalling that of viable cells [log10 (cfu ml−1) = 9.42] as was found prior to the drying process (log10 = 9.6). In the absence of mannitol, a survival was reduced by a factor of 104. Drying of cells at 20 °C led to higher survival rates than drying at 30 °C. Mannitol enhanced the survival rate at both
temperatures, and at both 20 °C and 30 °C the highest reduction in survival occurred when cells were dried at a water activity
of 0.76. In the presence of mannitol, differences in survival after drying at different water activities were less pronounced.
Rehydration of cells dried in the presence of mannitol resulted in an extended lag phase of 4 h compared to fresh cells. No
growth or acidification of the culture medium was observed for 12 h in the case of rehydrated cells dried in the absence of
mannitol. It was hypothesized that a radical scavenging activity of mannitol could partly explain these observations.
Received: 28 August 1998 / Accepted: 2 October 1998 相似文献
17.
The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating
tablet (RDT) of the taste-maske drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer
(Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content,
in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF
was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8∶2 did not show drug
release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption
ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and
disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch
F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1∶1 and 7% wt/wt Polyplasdone XL-10 showed
faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration
behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking
with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron
HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t90, 60 seconds) in SGF compared with marketed formulation (t90, 240 seconds;P<.01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets
in the oral cavity.
Published: June 22, 2007 相似文献
18.
Mamdouh M. Ghorab Heba M. Abdel-Salam Marwa A. El-Sayad Mohammed M. Mekhel 《AAPS PharmSciTech》2004,5(4):63-68
The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried
or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The
tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated
for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to
thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution
studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced
2-way crossover study. Phase-solubility studies indicated an AL-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory
flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation
showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD
in the formulations up to 30%. The mean pharmacokinetic parameters (Cmax, Ke, and area under the curve [AUC]0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam
tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between
tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving
the oral bioavailablity of meloxicam. 相似文献
19.
Bao-Jun Xu Qi-Jun Wang Xiao-Qin Jia Chang-Keun Sung 《Biotechnology and Bioprocess Engineering》2005,10(1):78-84
The purpose of this study was to optimize the solid state cultivation ofMonascus ruber on sterile rice. A single-level-multiple-factor and a single-factor-multiple-level experimental design were employed to determine
the optimal medium constituents and to optimize carbon and nitrogen source concentrations for lovastatin production. Simultaneous
quantitative analyses of the β-hydroxyacid form and β-hydroxylactone for of lovastatin were performed by the high performance
liquid chromatography (HPLC) method with a UV photodiode-array (PDA) detector. The total lovastatin yield (4≈6 mg/g, average
of five repeats) was achieved by adding soybean powder, glycerol, sodium nitrate, and acetic acid at optimal composition of
the medium increased by almost 2 times the yield observed prior to optimization. The experimental results also indicated that
the β-hydroxylactone form of lovastatin (LFL) and the β-hydroxyacid form of lovastatin (AFL) simultaneously existed in solid
state cultures ofMonascus ruber, while the latter was the dominant form in the middle-late stage of continued fermentation. These results indicate that optimized
culture conditions can be used for industrial production of lovastatin to obtain high yields. 相似文献
20.
Veluthakal R Wadzinski BE Kowluru A 《Apoptosis : an international journal on programmed cell death》2006,11(8):1401-1411
Emerging evidence suggests critical roles for protein phosphatase 2A (PP2A) in islet β cell function, including survival and
demise (Kowluru A: Biochemical Pharmacol 69:1681–1691, 2005). Herein, we identified an okadaic acid (OKA)-sensitive PP2A-like
phosphatase in the nuclear fraction from insulin-secreting INS-1 cells. Western blot analysis indicated relatively higher
abundance of the catalytic subunit of protein phosphatase 4 (PP4c) compared to PP2Ac in this fraction. Autoradiographic and
vapor-phase equilibration analyses suggested that the nuclear PP4c undergoes OKA-sensitive carboxylmethylation (CML) when
S-adenosyl-L-(3H-methyl) methionine (SAM) was used as the methyl donor. Exposure of INS cells to interleukin-1β (IL-1β; 600 pM; 48 h) resulted
in a marked increase in nitric oxide (NO) release with concomitant reduction in the degree of expression, the CML and the
catalytic activity of only PP4, but not PP2A, in the nuclear fraction. Immunoprecipitation studies suggested potential complexation
of PP4c with nuclear lamin-B, a key regulatory protein involved in the nuclear envelope assembly. Based on these findings,
we propose that IL-1β-mediated inhibition of PP4 activity might result in the retention of lamin-B in its phosphorylated state,
which is a requisite for its degradation by caspases leading to the apoptotic demise of the β cell (Veluthakal et al.: Am
J Physiol Cell Physiol 287:C1152–C1162, 2004).
Portions of this work were published in the abstract form in Diabetes [53; suppl 2; A377, 2004]. 相似文献